Devices, systems and methods for controlling conditions and delivery of substances

ABSTRACT

Embodiments of the present disclosure are directed to devices, systems, and methods for controlling environmental conditions for a volume of material. In some embodiments, a handheld, portable environmental control sleeve (ECS) is disclosed which is configured for controlling at least one environmental condition of a drug contained within a drug delivery or storage device (DDSD). The ECS includes an environmental control mechanism (ECM), thermal insulation material, at least one of a power source, a processor, at least one electrical contact, at least one indicator, at least one switch, at least one environmental condition sensor, a wireless transceiver, a phase change material and at least one heat dissipater. Upon the ECS receiving at least a portion of the DDSD, the at least one environmental condition of a drug contained within the DDSD is controlled by the ECM to be within a predetermined range.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims benefit of and priority to International PatentApplication No. PCT/US2015/040655, filed Jul. 15, 2015, which in turnclaims benefit of and priority to U.S. Provisional Patent ApplicationNos. 62/024,481 filed Jul. 15, 2014; 62/044,258 filed Aug. 31, 2014;62/053,823 filed Sep. 23, 2014; 62/077,918 filed Nov. 11, 2014;62/080,366 filed Nov. 16, 2014; 62/083,275 filed Nov. 23, 2014;62/086,689 filed Dec. 2, 2014; 62/097,087 filed Dec. 28, 2014;62/127,008 filed Mar. 2, 2015; 62/146,307 filed Apr. 12, 2015;62/150,567 filed Apr. 21, 2015; and 62/161,272 filed May 14, 2015. Thepresent application incorporates herein by reference the disclosures ofeach of the above-referenced applications in their entireties.

TECHNICAL FIELD

Some embodiments of the present disclosure generally relate to thecontrolling of substance environmental conditions and substancedelivery.

BACKGROUND

Drugs can be sensitive to environmental conditions such as light,humidity, temperature, pressure, atmosphere and other conditions. Manydrugs have limited boundaries to such conditions that if exceeded, candegrade the drug activity. Drugs that are exposed to environmentalconditions, which exceed certain limits, might lose their potency. Drugsthat are exposed to extreme environmental conditions might even turn tobe harmful, if used. For example, life maintaining drugs (e.g., insulin)can be exposed to extreme environmental conditions if left within avehicle, where temperatures can rise as high as 130 degree F. on asummer day. Similarly, upon a disaster situation (e.g., power outage,storm, and the like), drug delivery devices and pharmaceuticals may beexposed to harsh environmental conditions. In addition, drug deliverydevices and pharmaceuticals used for emergency events (e.g. earthquakes,hurricanes, wars) may require storage for extended periods of time,sometimes for over a year, without maintenance.

While devices exist that can maintain drugs and drug-containing deliverydevices under controlled environmental conditions, such current devicesare quite large and typically require a regular AC power supply fortheir operation, or large batteries of limited duration.

For example there are today mini-refrigerators used to keep drugs in acooled environment such as the Dison BC-170A mini insulin fridge fromZhengzhou Dison Electric Co.(http://www.medincn.com/sell_offers/104901/diabetic-portable-refrigerator-medicine-refrigerator-insulin-cooler.html).There are also other packs containing ice or devices which can cool thedrug based on water evaporation such as the FRIO® cooling wallet.

However these cooling packs do not control or stabilize the temperature,rather provide cooling to the entire pen injection device or drug vialor drug cartridge.

Injection devices similar to existing insulin pen injection devices forsingle use (such as the prefilled NovoLog FlexPenhttp://www.novolog.com/insulindiabetes/novologflexpen.aspx), or reusabledevices (such as the NovoPenhttp://www.novonordisk.com/diabetes_care/insulin_pens_and_needles/novopen_4/default.asp),have means to set the desired amount of drug to be injected. Suchdevices do not have means to control the environmental conditions of thedrug within the pen. When a drug is inside the pen, the drug must bekept in a refrigerator or in devices (e.g., Dison BC-170A mini insulinrefrigerator) for maintaining the drug under stable temperatureconditions.

SUMMARY OF SOME OF THE EMBODIMENTS

In some embodiments of the present disclosure, the environmentalconditions of any substance may be controlled and/or maintained. Thesubstance may comprise in a non-limiting example, a drug, a proteinbased substance, such as a protein based drug, a biological substance,such as hormones, a growth hormone, blood, body fluids, sperms, or eggs.The substance may comprise cosmetics, such as lipsticks, perfumes,toiletries, hair or skin care products, sprays, mousses, emulsions andgels, for example. The substance may comprise, resins, adhesives, glues,epoxy or cyanoacrylate glue. The substance may be configured in anysuitable form, such as a solid, liquid, emulsion, gas, gel, granule, andpowder, for example. Wherein the substance comprises a drug, the drugmay comprise any suitable form such as a solid, powder, tablet, pill,capsule, gas, gel, cream, emulsion, spray or a suppository, and may bedelivered in any suitable manner.

The substance may include more than one substance at the same ordifferent phase, such as, for example, a liquid mixed with anotherliquid or a liquid mixed with a powder. In some embodiments, keeping onecomponent of the mixture at a particular environmental conditionrequires a smaller amount of power than both components (e.g., keeping asmall amount of powder at a specific temperature).

In some embodiments, an environmental control apparatus is provided andincludes means to control the environmental conditions of a substance,such as a drug, contained in a container. Such apparatuses enable thecontrol of the environmental conditions of a small volume of asubstance, such as a drug with a volume, in a non-limiting example, of afew microliters and up to 10 milliliters, while requiring far lessenergy than having to maintain environmental control over a substancecontainer. This enables the maintenance of a substance in a substancecontainer for a substantially long time with little power requirements.For example, in some embodiments, environmental conditions required toproperly store the substance may be maintained as long as hours, days,weeks, months or even more than a year.

With many substances the long term storage environmental conditions(e.g., temperature) and short-term use environmental conditions, maydiffer. With respect to the latter, in some embodiments, the containermay be configured for switching between conditions. In use conditions,the conditions may be maintained for a shorter period of time than thelong term storage conditions.

In some embodiments, the environmental control apparatus may beconfigured to be relatively small, handheld and/or portable.

In some embodiments of the present disclosure there is provided ahandheld, portable environmental control sleeve (ECS) configured forcontrolling at least one environmental condition of a drug containedwithin a drug delivery or storage device (DDSD), the ECS includes anenvironmental control mechanism (ECM), thermal insulation material, andany two or more of: a power source, a controller, at least oneelectrical contact, at least one indicator, at least one switch, atleast one environmental condition sensor, a wireless transceiver, aphase change material and at least one heat dissipater. When the ECSreceives at least a portion of the DDSD, at least one environmentalcondition of a drug contained within the DDSD is controlled by the ECMto be within a predetermined range.

In some embodiments, the ECS is selected from the group consisting of: acylinder, a tube, a cap, and an oblong enclosure. The ECS mayencapsulate the DDSD or partially enclose a portion of the DDSD.

In some embodiments, the ECS shape is a cap and the interior of the capis configured to enclose at least a substantial portion of a drugreservoir of the DDSD. The cap may be reusable or disposable.

In some embodiments, the ECS is a tube configured to open and close suchthat the DDSD is contained therein.

In some embodiments, the ECS is configured for controlling at least twopredetermined ranges of the environmental condition. The ECS may beconfigured to switch from controlling a first predetermined range to thesecond predetermined range. The ECS may be configured to control atleast one environmental condition of a volume of less than or equal toabout 10 ml. The environmental condition may be automatically ormanually controlled.

In some embodiments, The ECS may further comprise at least onetemperature sensor configured to sense a temperature inside the ECSand/or at least one temperature sensor configured to sense a temperatureexternal to the ECS.

In some embodiments, the readings of a temperature sensor configured tosense a temperature inside the ECS and a temperature sensor configuredto sense a temperature external to the ECS, is used to determine theamount of drug in the DDSD or the amount of drug removed from the DDSD.

In some embodiments, the ECM may comprise a thermoelectric element (TEC)or a refrigerant-based heat pump or a heating and/or cooling element.

In some embodiments, the environmental condition is temperature and theECS may further include the power source and a temperature sensorconfigured to sense the temperature of the interior of the ECS. The flowof power from the power source to the ECM may be determined based upon atemperature of the interior of the ECS sensed by the temperature sensor.The temperature sensor may comprise a thermistor.

In some embodiments, the ECM may be configured to control theenvironmental condition of the drug contained in the DDSD upon theenvironmental condition being at least one of above and below apredetermined range. The environmental condition may comprisetemperature, and the ECM may be configured to perform at least one of:cooling the drug when the temperature inside the ECS is above thepredetermined range to a temperature within the predetermined range, andheating the drug when the temperature inside the ECS is below thepredetermined range, to a temperature within the predetermined range.

In some embodiments, the ECS may be configured to control the at leastone environmental condition according to at least one of: a firststorage state configured to retain the drug contained in the DDSD at theenvironmental condition within a first range, and a use state configuredto retain the drug contained in the DDSD at the environmental conditionwithin a second range. Prior to first use of the DDSD, the environmentalcondition of the drug may be maintained at the storage state. Afterfirst use of the DDSD, the environmental condition of the drug may bemaintained at the use state. The ECS may include a first switch. The usestate may be activated via the switch or automatically upon first use ofthe DDSD.

In some embodiments, the ECS may include at least one of a port and thewireless transceiver for communicating with at least a first device. TheECS may be configured to communicate with a remote device. The ECS maycomprise a phase-change material configured to aid in control of theenvironmental condition of a drug contained in the DDSD.

In some embodiments, the environmental condition is temperature andwherein the ECS may comprise a processor for controlling the ECM. Theprocessor may include computer instructions including an algorithmoperating thereon and configured to control the ECM. The algorithm maybe configured to automatically control the temperature of a drug storedwithin the DDSD and/or within the chamber within a predetermined range.The algorithm may control the temperature while minimizing a thermalload created by the operation of the ECM.

In some embodiments, the thermal insulation comprises INSULON® orsimilar constructed material. The phase-change material may be arrangedwithin the INSULON® material or external to the INSULON® material.

In some embodiments, the ECM is configured with a first side in thermalcontact with the interior of the ECS and a second side in thermalcontact with the heat dissipater. The ECM may be placed within any oneof the following: an aperture formed within the thermal insulationmaterial; or a thermal conducting area formed within the thermalinsulation material, the thermal insulation material may be formed ofwalls and an evacuated gap between the walls, wherein walls of thethermal insulation material are adjoined at an area of the thermalinsulation material to form the thermal conducting area.

The ECS may be configured to mechanically fit the DDSD.

In some embodiments of the present disclosure there is provided ahandheld, portable environmental control sleeve (ECS) configured forhousing at least a substantial portion of a drug delivery or storagedevice (DDSD), the ECS may comprise a thermal insulation material andmay be configured to control at least one environmental condition of adrug stored in the DDSD.

In some embodiments of the present disclosure there is provided a peninjection system for delivering a drug into tissue of a user. The systemmay comprise a drug injection pen having a drug reservoir containing adrug. The ECS may be configured as a cap for receiving at least asubstantial portion of the drug reservoir and controlling theenvironmental condition thereof. The ECS may further include at leastone of a port and a wireless transceiver for communicating with at leasta first device.

In some embodiments, the ECS includes the wireless transceiver and isconfigured to communicate with a remote device. The ECS may comprise aphase-change material configured to aid in control of the environmentalcondition of a drug contained in the DDSD.

In some embodiments, at least a portion of the DDSD comprises the drugreservoir configured to be in thermal contact with the ECM. The ECM maybe housed in the DDSD and is activated by a controller in the cap. Insome embodiments, the ECM is housed in the cap.

In some embodiments the ECM may be embedded within the injection pen orwithin the cap. In some embodiments, an activation element may beprovided and configured to activate the ECM which is part of the cap.The activation element may be housed in the injection pen or housed inthe cap.

In some embodiments of the present disclosure there is provided ahandheld, portable drug delivery device comprising an enclosure, a drugchamber for storing a drug, the chamber being arranged in proximity tothe enclosure and configured to be thermally shielded from theenclosure, an environmental control mechanism (ECM) configured tocontrol at least one environmental condition of the drug and optionallymonitor the environmental condition and a dispensing assembly. Thedispensing assembly may be configured to deliver the drug, retained inthe chamber, into a patient.

The dispensing assembly may comprise a needle and/or cannula configuredto be in fluid communication with the drug within the chamber anddeliver the drug into the patient. The dispensing assembly may comprisean opening configured for allowing removal of the drug from the chamberand delivering thereof to the patient via an orifice provided with thepatient. The chamber may be configured to retain a volume of less thanor equal to about 10 milliliters.

The device may comprise at least one of: a power source, a cannula orneedle for delivering the drug into the tissue, an optional transparentsection in the enclosure between the chamber and the needle, a settingmechanism for setting the drug amount for delivery to the tissue, andthe dispensing assembly for dispensing the drug from the chamber intothe tissue via the needle or cannula. The needle or cannula may beconfigured as an integral part of the delivery device.

In some embodiments, the chamber may be configured for insertion intothe delivery device prior to use. In some embodiments, the chamber maybe pre-loaded with the drug prior to use. The chamber may be configuredto reside within the enclosure, or may be configured for insertion intothe enclosure before use.

In some embodiments, the device may comprise a second chamber and amixing element. The second chamber may be thermally isolated from theenclosure or may be not thermally isolated from the enclosure. Thesecond chamber may contain a liquid portion of the drug.

In some embodiments, at least one environmental condition isautomatically controlled.

At least one temperature sensor may be configured to sense a temperatureof at least one of the inside of the chamber and the inside of theenclosure.

In some embodiments, the ECM comprises a thermoelectric cooler (TEC) ora refrigerant-based heat pump. In some embodiments, the environmentalcondition is a temperature of the drug. The device may further comprisesa power source for powering the ECM and a temperature sensor configuredto sense the temperature of at least one of the chamber and theenclosure. The flow of power from the power source to the ECM isdetermined based upon a temperature of at least one of the chamber andthe enclosure sensed by the temperature sensor. The ECM may beconfigured to control the environmental condition of the drug upon theenvironmental condition being at least one of above and below apredetermined range. For example, the environmental condition maycomprise temperature, and the ECM may cool the drug when the temperatureis above the range to a temperature within the range, and the ECM mayheat the drug when the temperature is below the range to a temperaturewithin the range.

In some embodiments, control of at least one environmental condition isaccording to at least one of: a first storage state configured to retainthe drug at the environmental condition within a first range, and a usestate configured to retain the drug at the environmental conditionwithin a second range.

In some embodiments, prior to first use of the device, the environmentalcondition of the drug is maintained at the storage state. After firstuse of the device, the environmental condition of the drug may bemaintained at the use state. The use state may be activated via a switchor automatically upon first use of the device.

In some embodiments, the device may comprise a drug-delivery pen. Thedevice may comprise insulation and may further comprise a phase-changematerial configured to aid in control of the at least one environmentalcondition of a drug stored in the chamber. The insulation may comprise aphase-change material configured to aid in control of the environmentalcondition of a drug stored in the chamber. The phase change material maybe configured to aid in the heating or cooling of a drug containedwithin the chamber and/or DDSD.

In some embodiments, at least one of the chamber and the enclosurecomprise INSULON® or similarly constructed material.

In some embodiments of the present invention there is provided a methodfor maintaining the efficacy of a drug over a period of time in aportable drug delivery device, the method comprising: providing a devicesuch as the ECS or the drug delivery device; and controlling the atleast one environmental condition via the ECM so as to maintain the drugat the at least one environmental condition.

In some embodiments, at least one environmental condition istemperature, and controlling of the temperature comprises either coolingor heating at least one of the drug and the area enclosing the drug.Controlling the environmental condition may be automatic or may bemanual.

The method may further comprise sensing a temperature of at least one ofthe drug and an area enclosing the drug via at least one temperaturesensor. The device may further comprise providing power from a powersource to the ECM based upon a temperature of at least one of the drugand the area enclosing the drug.

The method may further comprise controlling at least one environmentalcondition of the drug upon the environmental condition being above orbelow a predetermined range. Controlling the temperature may comprisecooling the drug via the ECM when the temperature is above the range toa temperature within the range and/or heating the drug via the ECM whenthe temperature is below the range to a temperature within the range.

Control of the environmental condition may be according to at least oneof: a first storage state configured to retain the drug at theenvironmental condition within a first range, and a use state configuredto retain the drug at the environmental condition within a second range.Prior to first use of the device, control of at least one environmentalcondition may comprise maintaining at least one environmental conditionof the drug at a storage state. After first use of the device, controlof the environmental condition comprises maintaining the environmentalcondition of the drug at a use state.

In some embodiments, the method may further comprise generating energyfrom the temperature gradient between at least one of the chamber, theenclosure and an outside environment external to the device. The energymay be generated via a thermoelectric element. The generated energy maybe stored in a battery for supplying power to the ECM.

In some embodiments, the method may further comprise communicatinginformation from the provided device to another device via at least oneof a port and a wireless transceiver. The device may comprise a remotedevice.

In some embodiments there is provided a handheld, portable environmentalcontrol apparatus configured for controlling at least one environmentalcondition of a substance contained within a substance containercomprising a substance chamber for containing the substance therein, theapparatus including an environmental control element comprising any oneof: thermal insulation material, or an active control element andthermal insulation material. When the apparatus is engaged with thecontainer at least one environmental condition of the substancecontained within the chamber is controlled by the environmental controlelement to be within a predetermined range. In some embodiments theenvironmental control element may be configured to perform both of:shifting the environmental condition of the substance, when theenvironmental condition inside the chamber is above the predeterminedrange, to an environmental condition within the predetermined range, andshifting the environmental condition of the substance, when theenvironmental condition inside the chamber is below the predeterminedrange, to the environmental condition within the predetermined range.

It should be appreciated that all combinations of the foregoing conceptsand additional concepts discussed in greater detail below (provided suchconcepts are not mutually inconsistent) are contemplated as being partof the inventive subject matter disclosed herein. In particular, allcombinations of claimed subject matter appearing at the end of thisdisclosure are contemplated as being part of the inventive subjectmatter disclosed herein and are considered only some of the numerousembodiments disclosed herein. It should also be appreciated thatterminology explicitly employed herein that also may appear in anydisclosure incorporated by reference should be accorded a meaning mostconsistent with the particular concepts disclosed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The skilled artisan will understand that the drawings primarily are forillustrative purposes and are not intended to limit the scope of theinventive subject matter described herein. The drawings are notnecessarily to scale; in some instances, various aspects of theinventive subject matter disclosed herein may be shown exaggerated orenlarged in the drawings to facilitate an understanding of differentfeatures. In the drawings, like reference characters generally refer tolike features (e.g., functionally similar and/or structurally similarelements).

The principles and operations of the systems, apparatuses and methodsaccording to some embodiments of the present disclosure may be betterunderstood with reference to the drawings, and the followingdescription. The drawings are given for illustrative purposes only andare not meant to be limiting.

FIGS. 1A and 1B are a schematic illustration of an exemplary substancecontrol system, at an assembled state (1A) and disassembled state (1B)according to some embodiments of the present disclosure;

FIG. 2 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 3 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 4 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 5 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 6 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 7 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 8 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 9 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 10 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 11 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 12 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 13 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 14 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 15 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 16 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 17 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIGS. 18A and 18B are a schematic illustration of an exemplary thermalswitch operative with a substance control system, shown in an activemode (FIG. 18A) and an inactive mode (FIG. 18B), according to someembodiments of the present disclosure;

FIGS. 19A and 19B are a schematic illustration of an exemplary thermalswitch operative with a substance control system, shown in an activemode (FIG. 19A) and an inactive mode (FIG. 19B), according to someembodiments of the present disclosure;

FIG. 20 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 21 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 22 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 23 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 24 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 25 is a schematic illustration of an exemplary substance controlsystem according to some embodiments of the present disclosure;

FIG. 26 is an exemplary graph showing the time span t it takes to effecta temperature change ΔT of water within the substance control system;

FIG. 27 is an exemplary graph showing the time t Vs. the calculatedquantity of the water shown in the example of FIG. 26;

FIG. 28 is an exemplary graph depicting the time t Vs. changes intemperature ΔT, per 1 unit of Insulin as measured in the substancecontrol system;

FIG. 29 is an exemplary flowchart illustrating a general process forexecuting an algorithm for repeated calculations of the substancequantity and processing thereof; and

FIG. 30 an exemplary flowchart illustrating a process for executing analgorithm for a single or few calculations of the substance quantity.

DETAILED DESCRIPTION

FIGS. 1A-6 illustrate an exemplary substance control system 100according to some embodiments of the present disclosure. The substancecontrol system 100 may include a substance container 104, for containinga substance within a substance chamber 106.

The substance may comprise in a non-limiting example, a drug, such asinsulin, a protein based substance, such as a protein based drug, abiological substance, such as hormones, a growth hormone, blood, bodyfluids, sperms, or eggs. The substance may comprise cosmetics, such aslipsticks, perfumes, toiletries, hair or skin care products, sprays,mousses, emulsions or gels, for example. The substance may comprise,resins, adhesives, glues, epoxy or cyanoacrylate glue. The substance maybe configured in any suitable form, such as a solid, liquid, emulsion,gas, gel, granules, or powder, for example. The substance may includemore than one substance at the same or different phase, such as, forexample, a liquid mixed with another liquid or a liquid mixed with apowder. Wherein the substance comprises a drug, the drug may include anysuitable forms such as a solid, powder, tablet, pill, capsule, gas, gel,cream, emulsion, spray or a suppository and may be delivered in anysuitable manner.

In some embodiments, the container 104 may comprise a drug deliverydevice or a drug storage device (DDSD), such as an injection pen 108shown in FIGS. 1A and 1B. In some embodiments, the injection pen 108 maybe a reusable injection pen configured for housing a replaceable drugcartridge comprising a drug 110, which is retained within the substancechamber 106. In some embodiments, the injection pen 108 may be aprefilled (or pre-loaded), disposable injection pen.

In a non-limiting example, the substance chamber 106 of the injectionpen 108 or any other container 104 may comprise a drug reservoir andencompass a volume of few microliters and up to 10 milliliters. In someembodiments the volume is up to about 1 milliliter. In some embodiments,the volume is about 10 milliliters or more than 10 milliliters. In someembodiments, the volume is less than 1 milliliter.

The container 104 may be configured in any suitable configuration forcontaining a substance therein. Some further exemplary containers andDDSDs for containing drugs may include a syringe, a drug vial (e.g. thevial shown in FIGS. 9-12), a drug cartridge (e.g. drug cartridge shownin FIGS. 13-15), an ampule (e.g. ampule shown in FIGS. 16-17), a pump(e.g. pump shown in FIG. 23), a pill box (e.g. pill box shown in FIG.24), and an inhalator, (e.g. inhalator shown in FIG. 25).

The injection pen 108 may include a drug dispensing assembly 114configured to deliver the drug 110 retained in the chamber 106 into auser (e.g. a human or animal patient). The drug dispensing assembly 114may comprise a plunger of a piston 118 or any suitable means to advancethe drug 110 to be delivered via a needle 120, which may be protected bya needle cover 122.

The piston movement may be adjusted in any suitable manner, such as by aunit injection setting knob 126. In another embodiment, piston movementmay be adjusted by manually applying pressure on the top of the piston118, such as in syringes, or pressure may be applied on the knob 126,such as in a jet injector.

In some embodiments, setting the desired drug dose in the injection pen108 may be performed by knob 126. Examples of such pens can be found inU.S. Pat. Nos. 6,454,746 and 8,663,167, each disclosure of which isincorporated herein by reference in its entirety. In some embodiments,the setting may be provided by a switch or any other electronic formatallowing a user to set a desired number, wherein the desired numbercorresponds to the amount of drug units to be injected.

The selected drug dose may be displayed by numerical display 130.

At least part of the injection pen 108 around the chamber 106 may betransparent to allow visual inspection of the drug solution in thechamber 106.

The substance, such as drug 110, may be required to be stored and/ordelivered at selected environmental conditions or at a range thereof. Anon-limiting example of the environmental conditions may includetemperature, light, humidity, and/or pressure.

The substance control system 100 may comprise an environmental controlapparatus 140 comprising an environmental control element 150 forcontrolling at least one environmental condition of the substance,including at least one of a temperature, light, humidity, and pressure.The environmental control element 150 may be configured to maintain orchange one or more such conditions of the substance to reach apredetermined selected condition. The environmental control element 150may additionally be configured to monitor the environmental condition.

The environmental control element 150 may comprise any suitablefunctionality for controlling and affecting one or more environmentalconditions of the substance, such as drug 110. For example, wherein thecondition is temperature, the environmental control element 150 mayinclude temperature controlling elements for maintaining a desiredtemperature, and/or for heating and cooling. The environmental controlelement 150 may include passive control elements and/or active controlelements. Non-limiting examples of active temperature controllingelements may include an environmental control mechanism (ECM) 162. TheECM 162 may comprise a micro-heat-pump/refrigerator configuration, suchas a magnetic configuration utilizing the Joule-Thomson expansionfunctionality or a mechanical configuration using a cooling gas, such asFreon, for example. Further active elements may include a thermoelectriccooling/heating element, a thermoelectric cooling element (TEC) or athermoelectric heat pump used for cooling and/or heating by utilizingthe Peltier effect, such as by controlling the flow of current/voltageto chamber 106.

Additional methods for removing/adding heat from/to the chamber 106 maybe used, including, for example, micro-fans and/or heat sink elements.

The active temperature controlling elements may be in communication witha power source, such as a battery 164, a controller and electronics 166,such as a thermistor, a transistor, boards, wires or circuitry, e.g. acontrol circuit for controlling the temperature controlling elements.Electrical connections (not shown) between the battery 164, and thecontroller and electronics 166 and the ECM 162 and any other electricalcomponent, may be provided.

In some embodiments, the environmental condition may be automaticallycontrolled via controller 166 or the environmental condition may bemanually controlled by the user.

In some embodiments, the battery 164 may be rechargeable. Recharging maybe performed via a recharging port 168, or via inductance or other meanswhich allow electrical charge generation.

In some embodiments, the ECM 162 (e.g. a TEC) may be in thermalcommunication with the chamber 106 or in proximity thereto, via athermal transmitter 170, formed in any suitable configuration. As seenin FIG. 1A, the ECM 162 is in thermal and/or mechanical contact with abase portion 172 of the thermal transmitter 170. The thermal transmitter170 may comprise a protruding portion 174 protruding from the baseportion 172. The protruding portion 174 may be engaged with the chamber106 and may be shaped as an elliptic paraboloid or any other suitableshape. The thermal transmitter 170 may be formed of any suitablethermally conducting material, such as aluminum, for example.

To further enhance thermal and/or mechanical contact between the thermaltransmitter 170 and the chamber 106, there may be provided thermalconductors 180 therebetween along at least a portion of the chamber 106or the container 104. The thermal conductor 180 may be formed of anysuitable material, such as a flexible thermally conducting material,e.g. a sponge thermal conductor, configured, when pressed by the thermaltransmitter 170, to facilitated thermal communication with the chamber106.

The environmental control apparatus 140 and/or the container 104 mayinclude at least one or more temperature sensitive elements comprisingsubstance temperature sensors 184, designed to monitor the temperatureof the chamber 106. In some embodiments, the chamber 106 may be made ofa material that is thermally conducting, such that the temperature ofthe chamber 106 is substantially similar to the temperature of thesubstance inside the chamber 106.

In some embodiments, the temperature sensor 184 may be configured tosense the temperature of the interior of the environmental controlapparatus 140 (e.g. the environmental control sleeve (ECS)) such thatthe temperature of the drug 110 contained in the container 104comprising the DDSD can be determined based on the temperature of theinterior of the ECS.

An additional ambient temperature sensor 186 or a plurality of sensors186 may be provided to monitor the ambient temperature outside theenvironmental control apparatus 140. In some embodiments, the ambienttemperature sensor 186 may be placed away from the environmental controlapparatus 140 and the container 104. The ambient temperature sensor 186may be configured to communicate with a tracking device or communicationdevice 250 and/or a central database 252, as will be further describedin reference to FIG. 2.

In a non-limiting example, the substance temperature sensor 184 and/orambient temperature sensor 186 may comprise a thermistor.

In an exemplary, non-limiting embodiment, a thermogenerator chip may bepositioned at one side thereof adjacent to chamber 106 for operating asthe substance temperature sensor 184, while the opposite side can beused to detect the temperature external to the container 104, therebyoperating as the ambient temperature sensor 186.

The ECM 162, such as the TEC, may generate heat during its operation. Aheat dissipater 190 may be provided and may be formed in any suitableconfiguration. In some embodiments, the heat dissipater 190 may comprisea heat sink or an active heat dissipater, such as a micro-fan.

In some embodiments, a cover 192 of the environmental control apparatus140 may at least partially or fully comprise the heat dissipater 190. Asseen in FIG. 1A, the cover 192 is formed partially of the heatdissipater 190 and partially of a plastic portion 194. The heatdissipater portion 190 may terminate at any suitable location along thecover 192, such as at a location overlying the ECM 162, or a locationoverlying thermal transmitter 170, a location overlying the chamber 106or any other section of the container 104. The remaining cover may beformed of the plastic portion 194 or any other suitable materiel.

The heat dissipater 190 may be formed of any suitable material, such asaluminum for dissipating heat from the ECM 162 to the ambientenvironment. The cover 192 may be formed with a smooth surface. Thecover 192 may additionally or alternatively be configured withformations thereon, such as knurls, notches, fins or corrugations forexample, so as to performing as miniature heat sinks thereon.

In some embodiments, the cover 192 may comprise recesses for allowingheat to dissipate to the ambient environment therethrough. In someembodiments, heat dissipating fins 196 or any other heat dissipatingelement may be provided on cover 192 or any other suitable location onthe environmental control apparatus 140.

It is appreciated that any embodiment of the environmental controlapparatus 140 of FIGS. 1A-25 may comprise the heat dissipating fins 196or any other heat dissipating elements.

The cover 192 may be formed of an opaque material for preventingpenetration of light therein.

A non-limiting example of a passive temperature controlling elementincludes thermal insulation 200, also referred to as thermal isolation,formed of any suitable insulating material. The thermal insulation 200may be placed intermediate the cover 192 and the chamber 106 forpreventing uncontrolled changes in the substance temperature.

In some embodiments, thermal insulation 200 may be realized by amulti-layered material, formed of walls 202 and 204. A gap 206 definedby a space between the walls 202 and 204 may be, at least partially,evacuated. In a non-limiting example, such a thermal insulationconfiguration including the multi-layered material formed of walls 202and 204 and evacuated gap 206, may be commercially available asINSULON®, made by Concept Group, Inc. (www.conceptgroupinc.com), as wellas similar constructions disclosed in U.S. Publication No. 20140090737,incorporated herein by reference in its entirety. The walls 202 and 204may be formed of stainless steel, such as stainless steel 340. Walls 202and 204 may be vacuum brazed at both edges with the gap 206 in betweenthe layers. In some embodiments, this gap 206 may be formed with a widthof about 0.6 mm, however the gap 206 may be smaller or larger. In someembodiments, the gap width may range from about 0.3-5 mm. In someembodiments, the gap width may range from about 0.6-3 mm.

In some embodiments, the vacuum within the gap 206 may be relativelyhigh, such as about 10⁻⁹ torr, in a non-limiting example.

Further insulating materials, such as a thermal insulating foam 212 maybe provided intermediate the cover 192 and the chamber 106.

Air tight encapsulation of the container 104 within the environmentalcontrol apparatus 140 may be provided for preventing exposure tohumidity. In some embodiments, a brush 216 or any other flexiblematerial may be placed at least partially intermediate the environmentalcontrol apparatus 140 and the container 104. The brush 216 may preventformation of air pockets during insertion and removal of the container104 into and from the environmental control apparatus 140.

In some embodiments, a thin layer of a phase change material may beprovided around the container 104. The phase change material may beconfigured to change from a liquid phase to a solid phase for creatingan air gap that allows removal of the container 104 from theenvironmental control apparatus 140. After insertion of the container104 back into the environmental control apparatus 140, the phase ischanged to a liquid phase for removal of the air gap.

In some embodiments, the environmental control apparatus 140 maycomprise additional layers of a phase change material as will be furtherdescribed in reference to FIG. 2. The phase-change material (PCM) mayinclude a substance with relatively high heat of fusion which, bymelting and solidifying at a specific temperature, is capable ofabsorbing, storing and releasing relatively large amounts of energy.

The environmental control apparatus 140 and/or the container 104 maycomprise one or more detectors 218 for detecting one or moreenvironmental conditions of the substance (e.g. drug 110), such as thedrug temperature, as described above, or any other parameter of the drug110, such as color, clarity or transparency, for example.

In some embodiments, the clarity of the substance may be detected, bytransmitting light through the chamber 106 and detecting the lightattenuation by detector 218. The clarity of a drug may be indicative ofthe drug efficacy. For example, the efficacy of insulin may be reducedwhen the drug is cloudy.

The detector 218 may be configured to detect use of the substance (e.g.drug 110), such as the last time the drug was dispensed from thecontainer 104 and/or the last time the container 104 was opened. Thedetection of use of the substance may be performed in any suitablemanner by detecting any change in the container 104 associated withdispensing the substance. In a non-limiting example, the release of theneedle cover 122 prior to delivery of the drug 110 may be detected andindicate use of the drug 110. In some embodiments, wherein the peninjector 108 is configured with a removable cartridge, the removal of anexisting cartridge and/or insertion of a new cartridge may be detectedand indicative of use of the drug 110.

In some embodiments, the movement (e.g. pressing or turning) of thesetting knob 126 may be detected by detector 218 and may be indicativeof preparation of the substance for use.

In some embodiments, during removal of the container 104 from theenvironmental control apparatus 140 the detachment of the protrusion 256(see insert in FIG. 1A) of environmental control apparatus 140 from thematching recess 258 of container 104 may be detected by detector 218 andmay be indicative of preparation the substance for use.

In some embodiments, the detector 218 may be configured to detectreflection of light from the container and/or the environmental controlapparatus 140, such that the changes in the reflection may be indicativeof use of the substance. For example, during the storage state, the cap230 (FIG. 1A) or tube 240 (FIG. 2) may cover the chamber 106 andtherefore there is no reflection of light from the substance. Inshifting to the use state, the cap 230 or tube 240 may be removed,thereby exposing the substance to light, which reflection may bedetected.

In some embodiments, the environmental control apparatus 140 and/or thecontainer 104 may comprise a counter or timer 220 for detecting theduration of time since previous use of the substance, such as theprevious delivery of the drug, for example.

The quantity of used substance, such as the dose of the delivered drug110, as well as the quantity of substance remaining in the container 104following use, may be detected in any suitable manner, such as bymethods described in reference to FIGS. 26-30.

The environmental control apparatus 140 and/or the container 104 maycomprise one or more indicators 222, such as LED indicators or a smallelectronic display for example. The indicators 222 may indicate one ormore environmental conditions of the substance (e.g. drug 110), such asthe drug temperature, or any other parameter of the drug 110, such ascolor, clarity or transparency, for example.

The indicator 222 may be configured to indicate use of the substance,the quantity of the used substance, the time the substance was lastused, the last time the container 104 was opened and/or past occurrencesof use of the substance. The indicator 222 may be configured to indicatethe history of the substance, such as to indicate past deviations fromthe required temperature range. The indicator 222 may also be configuredto indicate other parameters related to the container 104 or theenvironmental control apparatus 140, such as the remaining batterypower.

In some embodiments, the environmental control apparatus 140 maycomprise the ECS configured for controlling at least one environmentalcondition of a drug contained within the DDSD. The ECS may include theECM 162. In some embodiments, the ECS may include one or more of a powersource (e.g. battery 164), a controller 166, at least one electricalcontact, at least one indicator 222, at least one switch (e.g. stateswitch 800 or thermal switch 650 of FIGS. 18A-19B), at least oneenvironmental condition sensor (e.g. sensor 184), a wireless transceiver(e.g. communication means 248), a phase change material (e.g. phasechange material layer 260 of FIG. 3) and at least one heat dissipater(e.g. heat dissipater 190).

The ECS may be configured to receive at least a portion of the DDSD. Atleast one environmental condition of the drug 110 contained within theDDSD may be controlled by the ECM 162 to be within the predeterminedrange.

In some embodiments, the ECS may be shaped to mechanically fit the DDSD.For example, the ECS may be formed as a cap, (e.g. cap 230 of FIGS. 1Aand 1B) insertable on a DDSD. The ECS may be formed as a tube (e.g. tube240 of FIG. 2) for receiving the DDSD. In some embodiments, the ECS maybe shaped to mechanically fit the chamber 106 within the DDSD (e.g. theenclosure 356 of FIG. 7). In some embodiments The ECS may be shaped tomechanically fit the DDSD and to be at least partially inserted therein(e.g. the ECM 162 and base 610 mechanically fitting the ampule 580 ofFIG. 16).

In some embodiments, the ECS may be configured to encapsulate the DDSD,e.g. tube 240 of FIG. 2, or may be configured to at least partiallyenclose a portion of the DDSD, e.g. cap 230 of FIGS. 1A and 1B, whereinthe interior of the cap is configured to enclose at least a portion of adrug reservoir of the DDSD or enclosure 356 of FIG. 7 enclosing thechamber 106 of the DDSD.

The ECS may be configured in any suitable shape or form such as acylinder, a tube, a cap, an oblong enclosure, or an enclosure, forexample.

As seen in FIGS. 1A and 1B, the environmental control apparatus 140comprising the ECS may be formed in any suitable configuration, such asa cap 230 insertable on at least a portion of the container 104, as seenin FIGS. 1A and 1B or as a ring or jacket enclosing the container 104.

In some embodiments, the cap 230 may be configured to replace anexisting, conventional cap of a conventional container, such as theinjection pen 108. In some embodiments, the cap 230 may be configured tobe inserted over an existing, conventional cap of the container 104.

Turning to FIG. 2, it is seen that the environmental control apparatus140 of FIGS. 1A and 1B may be formed as a tube 240. The tube comprises adetachable first portion 242 and second portion 244 formed for insertionof the environmental control apparatus 140 therein and removaltherefrom. In the embodiment of FIG. 2, the first portion 242 maycomprise the ECM 162, such as the TEC or any other active temperaturecontrolling element, as well as the thermal transmitter 170 and thermalconductors 180. The second portion 244 may comprise the battery 164 andthe controller and electronics 166, it being appreciated that thecomponents of the environmental control apparatus 140 may be placed atany suitable location. In some embodiments, the first portion 242 andsecond portion 244 comprise the thermal insulation 200.

Heat may be dissipated by heat dissipater 190 forming at least a portionof a cover 246 of tube first portion 242. In some embodiments, cover 246may further comprise heat dissipating fins 196 or any other heatdissipating element. A cover 247 of the second portion 244 may be formedof plastic or any other suitable material. The first portion 242 mayterminate at any suitable location parallel to the container 104, suchas at a location overlying the chamber 106 or any other section of thecontainer 104.

The first portion 242 may be engaged with second portion 244 in anysuitable manner, such as by a threaded engagement or a snap-fitengagement, for example.

In some embodiments, the first portion 242 may be configured to replacean existing, conventional cap of a conventional container, such as theinjection pen 108, and second portion 244 may be engaged with the firstportion 242. In some embodiments, the first portion 242 may beconfigured to be inserted over an existing, conventional cap of thecontainer 104 and second portion 244 may be engaged with the firstportion 242.

As seen in FIG. 2, the environmental control apparatus 140 and/or thecontainer 104 may be configured for transmitting information fromcomponents thereof by wireless or wired communication means 248. Theinformation may be related to the environmental condition of thesubstance or any other information related to the substance controlsystem 100. In a non-limiting example, sensors or detectors (e.g.sensors 184 and/or 186) may be configured to detect a signal and/or anydata relating to the operation or use of the substance control system100. Such signal/data may be transmitted via the wireless or wiredcommunication means 248 to a tracking or communication device 250, to acentral database 252, and/or from the device 250 to the central database252. The transmission may be performed in any suitable manner, such aswirelessly, via an analog short range communication mode, or a digitalcommunication mode including WIFI or Bluetooth or cellular means, or viaa wired connection or to any remote device to forward the collecteddata. Additional examples for transmission may be via a network. Thenetwork may comprise, the cloud, a local area network (LAN), a wide areanetwork (WAN), or a global network, for example. The network may be partof, or comprise any suitable networking system, such as the Internet,for example, or Intranet. Generally, the term “Internet” may refer tothe worldwide collection of networks, gateways, routers, and computersthat use Transmission Control Protocol/Internet Protocol (“TCP/IP”) andother packet based protocols to communicate therebetween.

In some embodiments, the device 250 may comprise at least one of aremote device, a computer, a cellular phone, smartphone, a tablet,and/or desktop mobile device. In some embodiments, the device 250 maypair with the environmental control apparatus 140 by imaging a LEDindicator formed on the environmental control apparatus 140 or by anyother identification mechanism.

The central database 252 may comprise any suitable device or functionfor storage of the data and/or analysis thereof. The central databasemay comprise a processor and/or memory. In a non-limiting example, thecentral database 252 may comprise at least one of a computer, PC,laptop, tablet, smartphone, media player and other mobile or desktopdevice.

The data may be used by a physician, caretaker or the user (e.g.patient) to track the administration of the substance, e.g. drug 110.Additionally, the data may be used to alert the user upon deviation fromthe predetermined environmental condition range or threshold.Additionally, the data may be used to alert the user upon reduction ofthe efficacy of the drug 110 due to excess heat or any other relevantenvironmental condition and/or parameter, such as upon passage of thedrug expiration date, for example. Moreover, the data may be used toinform the user the time the substance was last used, the quantity ofused substance, the last time the container 104 was opened and/or pastoccurrences of use of the substance. Furthermore, the data may be usedto inform the user the next time the substance is to be used andpossibly the quantity that needs to be used. The information and alertmay be provided in any suitable manner such as by an optical or audialsignal.

In some embodiments, the data may be used to monitor delivery of drugsin various geographical locations. For example, whereupon drugs 110 areto be transported to a multiplicity of locations, e.g. by a globalhealth organization, or a pharmaceutical distributor, the data may beused to monitor the location of the drug delivery device, such as by aGPS element provided in the substance control system 100.

In some embodiments, an alert may be transmitted to an appropriateentity in case of an undesired deviation from predeterminedenvironmental conditions or the predetermined location. The alert and/ormonitoring may be performed for a single environmental control apparatus140 and/or container 104 in a single location, or for a plurality ofenvironmental control apparatuses 140 and/or containers 104 in a singlelocation or in a plurality of locations.

In some embodiments, the environmental control apparatus 140 may beconfigured to track the type of substance (e.g. drug 110) placed withinthe container 104. For example, the environmental control apparatus 140may include a passive electronic ID thereon (e.g., RFID), and an IDreader. Through the communication means 248, the environmental controlapparatus 140 may be connected by wire or wirelessly via a network tothe device 250 and/or to central database 252 to forward the collecteddata indicative of the substance type.

Any one of the embodiments of the environmental control apparatus 140 ofFIGS. 1A-25 may be configured for transmitting information therefrom tothe device 250 and/or central database 252.

In some embodiments, the environmental control apparatus 140 and/or thecontainer 104 may comprise an identification element. The environmentalcontrol apparatus 140 may be configured to detect the identificationelement placed on a container 104. In some embodiments, an environmentalcontrol apparatus 140 may be configured to operate with a selectedcommercial brand of container 104. The identification element may beused to allow activation of the environmental control apparatus 140 uponidentification of the selected container 104.

The identification element may comprise an RFID element, an electricalelement, such as a wire or a sensor and/or a mechanical element, such asan activation pin or an identification element 254. The identificationelement 254 (FIG. 1A) may comprise a feature shaped as a protrusion 256protruding from the environmental control apparatus 140 and configuredto match a recess 258 formed on the container 104 (or vice versa).

FIGS. 3 and 4 each illustrate an exemplary substance control system 100according to some embodiments. As seen in FIGS. 3 and 4, theenvironmental control element comprises passive temperature controllingelements, such as a layer of thermal insulation 200.

The cover 192 of the environmental control apparatus 140 may be formedof any suitable material, such as plastic. The cover 192 may be formedof an opaque material for preventing penetration of light therein.

In some embodiments, the environmental control apparatus 140 maycomprise a phase change material formed as a layer 260 underlying, atleast partially, a layer of the thermal insulation 200. The phase changematerial layer 260 further absorbs heat flux which may pass through thethermal insulation 200 before it reaches the substance (e.g. drug 110).The phase-change material is configured to aid in control of theenvironmental condition of the substance (e.g. drug 110) contained inthe container (e.g. the DDSD).

In some embodiments, the phase change material layer 260, may bearranged within the thermal insulation 200, such as within the gap 206of the INSULON® material or a similar constructed material or outside ofthe INSULON® material.

As seen in FIGS. 3 and 4, the container 104 comprises the injection pen108. In FIG. 3, the environmental control apparatus 140 is formed as acap 266 insertable on at least a portion of the container 104. In someembodiments, the environmental control apparatus 140 may be formed as aring or jacket enclosing the container 104 or any other suitableconfiguration, such as a tube 270 shown in FIG. 4. In the embodiment ofFIG. 4 the tube 270 comprises a first portion 272 and a second portion274. The first portion 272 and the second portion 274 may comprise theenvironmental control element 150 including the layer of thermalinsulation 200 and the phase change material layer 260, it beingappreciated that the components of the environmental control apparatus140 may be placed at any suitable location.

In some embodiments, the phase change material layer 260 is obviatedfrom the environmental control apparatus 140 of FIGS. 3 and 4 and theenvironmental control element 150 may comprise thermal insulation 200only.

FIG. 5 illustrates an exemplary substance control system 100 accordingto some embodiments of the present disclosure. As seen in FIG. 5, theenvironmental control apparatus 140 may comprise a tube 278 including aninsulating construction 280 formed of at least two mutually insertableinner and outer insulating enclosures 284 and 286. The inner insulatingenclosure 284 may be formed in a cup-like shape and inserted into theoppositely facing outer insulating enclosure 286, formed in a cup-likeshape as well. Insulating enclosures 284 and 286 may each comprise amulti-layered material, formed of walls 202 and 204 wherein vacuum isestablished between the gap 206 formed therebetween. A sealing element290, such as a gasket or an O-Ring, may be placed between the insulatingenclosures 284 and 286 to insure an inner space enveloped between thetwo insulating structures 284 and 286 is sealed from the ambientenvironment.

In the absence of the outer insulating enclosure 286, heat mayinfiltrate into the environmental control apparatus 140 around an edge288 of the inner insulating enclosure 284 and reach the container 104.The configuration of the two mutually insertable, oppositely facinginner and outer insulating enclosures 284 and 286, may prevent thisinfiltration of heat.

The walls 202 and 204 of inner and outer insulating enclosures 284 and286 may extend along the container 104 to any suitable length, such asparallel to the injection pen 108 and extending over the needle cover122, as seen in FIG. 5. In some embodiments, the walls 202 and 204 maypartially overlay the entire chamber 106 or a portion thereof or mayterminate prior to the chamber 106.

In some embodiments, the inner insulating enclosure 284 may be placedoutwardly and the outer insulating enclosure 286 may be placed withinthe inner insulating enclosure 284.

In some embodiments, the environmental control apparatus 140 of FIG. 5may further include the phase change material layer 260 shown in FIG. 3,placed at any suitable location, such as intermediate the insulatingconstruction 280 and the container 104.

FIG. 6 illustrates an exemplary substance control system 100 accordingto some embodiments of the present disclosure. As seen in FIG. 6, theenvironmental control apparatus 140 may be formed as a tube 300enclosing the container 104. The tube 300 may comprise a detachablefirst portion 312 and a second portion 314. In the embodiment of FIG. 6the first portion 312 may comprise the ECM 162 and the second portion314 may comprise the battery 164 and the controller and electronics 166,it being appreciated that the components of the environmental controlapparatus 140 may be placed at any suitable location. The ECM 162 maycomprise the thermoelectric cooling/heating element.

The ECM 162 is in contact with the base portion 172 of the thermaltransmitter 170. The protruding portion 174 is engaged with the chamber106. The thermal conductors 180 may be provided along at least a portionof the chamber 106 or the container 104. Electrical connections (notshown) between the battery 164, and the controller and electronics 166and the ECM 162 and any other electrical component are provided.

The environmental control apparatus 140 and/or the container 104 mayinclude at least one or more substance temperature sensors 184 and/or atleast one or more ambient temperature sensors 186.

In some embodiments, the first portion 312 and second portion 314comprise the thermal insulation 200. The thermal insulation 200 may beformed in any suitable configuration, such as comprising the insulatingconstruction 280 including the two mutually insertable inner and outerinsulating enclosures 284 and 286, as described in reference to FIG. 5.

Thermal conductivity between the ECM 162 and the chamber 106 may beprovided in any suitable manner. In the embodiment of FIG. 6, thethermal conducting walls 202 and 204 of the outer insulating enclosure286 may be adjoined at to create thermal contact therebetween at athermal conducting area 320 adjacent to the ECM 162. Thus the thermalinsulation 200 is excluded at area 320 allowing thermal conduction fromthe ECM 162, via adjoined walls 202 and 204 and thermal transmitter 170,to chamber 106. In some embodiments, walls 202 and 204 may be formedwith an aperture at area 320, thereby excluding the thermal insulation200 at area 320 and allowing thermal contact between the ECM 162 and thethermal transmitter 170.

In some embodiments, the environmental control apparatus 140 maycomprise the phase change material formed as an inner layer 324underlying at least partially a layer of the thermal insulation 200 forfurther absorbing heat flux (e.g. from the ambient environment or fromthe ECM 162) which may pass through the thermal insulation 200 before itreaches the substance.

In some embodiments, an outer layer 326 of a phase change material maybe provided intermediate at least a portion of the thermal insulation200 and a cover 330 of tube first portion 312. The outer phase changematerial layer 326 may be provided to absorb the heat flux generated bythe ECM 162. In some embodiments, the phase change material layer 326may comprise multiple phase change materials, wherein each phase changematerial is configured with a different phase change temperaturethreshold, thereby allowing the phase change material layer 326 absorbthe heat fluxes generated at different temperatures.

Heat may be dissipated by heat dissipater 190 forming at least a portionof cover 330 of tube first portion 312, which in some embodiments mayfurther comprise heat dissipating fins 196 or any other heat dissipatingelement. A cover 332 of the second portion 314 may be formed of plasticor any other suitable material. The first portion 312 may terminate atany suitable location parallel the container 104, such as at a locationoverlying the chamber 106 or any other section of the container 104.

The first portion 312 may be engaged with second portion 314 in anysuitable manner, such as by a threaded engagement or a snap-fitengagement, for example.

The environmental control apparatus 140 of any of FIGS. 1A-25, may bereusable or disposable or may comprise both a reusable and a disposableportion. The container 104 may be configured for single use, such as anampule (FIG. 16) or for multiple use, such as a refillable injectionpen.

The environmental control apparatus 140 of any of FIGS. 1A-25 may beformed as a handheld, portable device.

In any of the embodiments of FIGS. 1A-25 the power source may compriseenergy harvesting devices configured to generate energy which canfurther be stored. Combining such energy harvesting devices inapparatuses 140 that require the battery 164 to operate, may reduce thebattery size. In some embodiments, the energy harvesting device may beused to recharge the battery 164 based on the temperature gradientbetween the temperature within chamber 106 and the ambient environmenttemperature external to the environmental control apparatus 140. Theenergy stored in the battery 164 may be used to control the temperature.In some embodiments, a thermogenerator chip may be used for generatingenergy exploiting very low temperature differences (e.g. 5 C.°). Such achip may be, for example, commercially available as a MPG-D655 chip fromMicropelt (http://www.micropelt.com). Additionally, the power source maycomprise an element used for energy storage and incorporated in anelectrical circuit. An exemplary energy storage device may becommercially available as the NanoCap by Dais Analytic Corporation of11552 Prosperous Drive Odessa, Fla. 33556, U.S.A(http://www.daisanalytic.com/applications/nanocap.html).

In any of the embodiments of FIGS. 1A-25 the environmental control ofthe substance is targeted to the chamber 106, such that other componentswithin the container 104 are not controlled. For example, in theinjection pen 108 of FIG. 1A, the chamber 106 is heated or cooled by theECM 162 while the piston 118 remains uncontrolled. This targeted controlallows the environmental control apparatus 140 to operate usingsignificantly less energy than would have been required if the entirecontainer 104 were heated/cooled.

The environmental control apparatus 140 of the embodiments of FIGS. 1A-6are configured to be inserted on the container 104. In some embodiments,the environmental control apparatus 140 may be housed within thecontainer 104, such as shown in FIGS. 7 and 8.

FIGS. 7 and 8 are each a schematic illustration of an exemplarysubstance control system according to some embodiments of the presentdisclosure.

As seen in FIG. 7, the container 104 comprises an injection pen 350including the chamber 106 containing the drug 110 therein. The injectionpen 350 may be disposable or reusable. The environmental controlapparatus 140 may be placed within the container 104 around the chamber106 or in proximity thereto and may be configured to control andmaintain the environmental conditions of the substance within thechamber 106.

The environmental control apparatus 140 may comprise an enclosure 356including the ECM 162 comprising the TEC or any other active temperaturecontrolling element. The enclosure 356 may be formed of the thermalinsulation 200. In some embodiments, the thermal insulation 200 maycomprise the multi-layered material, formed of walls 202 and 204 withthe evacuated gap 206 therebetween. The ECM 162 may be placed at anysuitable location for thermal and/or mechanical contact with the chamber106. As seen in FIG. 7, the ECM 162 is mounted within an aperture 370formed within the enclosure 356, thereby excluding the thermalinsulation 200 at the aperture 370 and allowing thermal contact betweenthe ECM 162 and the chamber 106.

The battery 164 and the controller and electronics 166 may be embedded,or otherwise contained, within the enclosure 356 or within the injectionpen 350, or within a cap 360 covering the injection pen 350, as shown inFIG. 7. The cap 360 may comprise electrical contacts 366 for electroniccommunication with corresponding electrical contacts 368 of theenclosure 356.

At least one or more substance temperature sensors 184 may be providedin proximity to the chamber 106 and/or at least one or more ambienttemperature sensors 186 may be provided in proximity to the ambientenvironment at any suitable location, such as on the injection pen 350or cap 360.

The detectors 218, timers 220 and/or indicators 222 may be placed on cap360, as seen in FIG. 7, or on the enclosure 356 or on the injection pen350.

Heat may be dissipated by heat dissipater 190 forming at least a portionof a cover or ring 380 surrounding the pen injector 350. In someembodiments, heat dissipating fins 196 or any other heat dissipatingelement may be provided. In some embodiments, the heat dissipater 190may comprise a heat sink 390 placed within the pen injector 350. Theheat may be removed from the ECM 162 via the piston 118 configured forconducting heat to heat sink 390. Additional methods for removing/addingheat from/to the chamber 106 may be used, including, for example,micro-fans and/or heat sink elements. A micro-fan 394 may be placedwithin the container 104.

In some embodiments, the cap 360 is formed, at least partially, with alayer of thermal insulation 200.

As seen in FIG. 8, the container 104 comprises the injection pen 350comprising the chamber 106 containing the drug 110 therein. Theinjection pen 350 may be disposable or reusable.

The environmental control apparatus 140 may be placed within thecontainer 104 around the chamber 106, or in proximity thereto and may beconfigured to control and maintain the environmental conditions of thesubstance within the chamber 106.

The environmental control apparatus 140 may comprise an enclosure 396including the environmental control element 150 comprising the layer ofthermal insulation 200 for shielding the chamber 106 from the ambientenvironmental conditions. As described in reference to FIG. 1A, thethermal insulation 200 may be realized by the multi-layered material,formed of walls 202 and 204. The gap 206 defined by a space between thewalls 202 and 204 may be, at least partially, evacuated. The phasechange material layer 260 may be provided and, at least partially,underlie the thermal insulation 200.

In some embodiments, the phase change material layer 260 is obviatedfrom the environmental control apparatus 140 of FIG. 8 and theenvironmental control element 150 may comprise the thermal insulation200 only.

FIGS. 9-12 are each a schematic illustration of an exemplary substancecontrol system according to some embodiments of the present disclosure.

As seen in FIGS. 9 and 10, the container 104 comprises an ampule or vial400 including the chamber 106 containing a substance therein. The vial400 may be a drug vial for single or multiple use and may be disposableor reusable.

In FIGS. 9 and 10, the environmental control apparatus 140 may be formedas a tube 410 comprising a detachable first portion 412 and secondportion 414.

The first portion 412 may be engaged with second portion 414 in anysuitable manner, such as by a threaded engagement or a snap-fitengagement, for example.

In the embodiments of FIG. 9 the first portion 412 may comprise the ECM162 and the second portion 414 may comprise the battery 164 and thecontroller and electronics 166, it being appreciated that the componentsof the environmental control apparatus 140 may be placed at any suitablelocation. The ECM 162 may comprise the TEC or any other activetemperature controlling elements

Electrical connections (not shown) between the battery 164, and thecontroller and electronics 166 and the ECM 162 and any other electricalcomponent are provided.

The thermal conductor 180 (FIG. 1A) and/or brushes 216 may be provided.

The environmental control apparatus 140 and/or the container 104 maycomprise one or more detectors 218, timers 220 and/or indicators 222.

The environmental control apparatus 140 and/or the container 104 mayinclude at least one or more substance temperature sensors 184 and/or atleast one or more ambient temperature sensors 186.

In some embodiments, as seen in FIG. 9, the first portion 412 and secondportion 414 comprise the thermal insulation 200. The thermal insulation200 may be formed in any suitable configuration, such as a layer ofinsulating material 420 at least partially underlying a cover 430 and432 of respective first and second portions 412 and 414. The ECM 162 ismounted within an aperture 440 formed within the insulating material420, thereby excluding the thermal insulation 200 at the aperture 440and allowing thermal contact between the ECM 162 and the chamber 106.

In some embodiments, as seen in FIG. 10, the thermal insulation 200 maycomprise the insulating construction 280 including the two mutuallyinsertable inner and outer insulating enclosures 284 and 286, asdescribed in reference to FIG. 5. Thermal conductivity between the ECM162 and the chamber 106 may be provided in any suitable manner. In theembodiment of FIG. 10, the thermal conducting walls 202 and 204 of theouter insulating enclosure 286 may be adjoined to create thermal contacttherebetween at a thermal conducting area 444 adjacent to the ECM 162.Thus excluding the thermal insulation 200 at area 444 and allowingthermal conduction from the ECM 162, via adjoined walls 202 and 204 tochamber 106.

In some embodiments, the environmental control apparatus 140 maycomprise the phase change material formed as an inner layer 450underlying, at least partially, a layer of the thermal insulation 200for further absorbing heat flux (e.g. from the ambient environment orfrom the ECM 162) which may pass through the thermal insulation 200before it reaches the substance.

In some embodiments, an outer layer 454 of a phase change material maybe provided intermediate at least a portion of the thermal insulation200 and the cover 430. The outer phase change material layer 454 may beprovided to absorb the heat flux generated by the ECM 162. For example,whereupon the ECM 162 comprises the TEC, the TEC generates heat duringoperation. The outer phase change material layer 454 is provided toassist the heat dissipater 190 to absorb heat from the TEC.

The phase change temperature threshold is the temperature whereupon thephase change material changes its phase. In some embodiments, thethreshold temperature of the inner phase change material layer 450 maybe selected to ensure the drug 110 will not be heated more than thepredetermined temperature range. In some embodiments, the thresholdtemperature of the outer phase change material layer 454 may be selectedsuch that the phase change material layer 454 will absorb the heat fluxto be dissipated by the heat dissipater 190 and yet will remainunaffected by the temperature of the ambient environment.

In some embodiments, the phase change material layer 454 may comprisemultiple phase change materials, wherein each phase change material isconfigured with a different phase change temperature threshold, therebyallowing the phase change material layer 454 to absorb the heat fluxesgenerated at different temperatures.

Heat may be dissipated by heat dissipater 190 forming at least a portionof the cover 430 of tube first portion 412, which in some embodimentsmay further comprise heat dissipating fins 196 or any other heatdissipating element. The cover 432 of the second portion 414 may beformed of plastic or any other suitable material. The first portion 412may terminate at any suitable location parallel the container 104, suchas at a location overlying the chamber 106 or any other section of thecontainer 104.

In some embodiments of FIGS. 9 and 10 or any of FIGS. 1A-25, theenvironmental control apparatus 140 may comprise a shock absorber 460for absorbing mechanical shock so as to protect the substance duringaccidental dropping of the container 104.

The environmental control apparatus 140 may be configured with apress-to-release mechanism 464 typically placed on cover 430 or 432 forease of removal of the vial 400 from the environmental control apparatus140 and insertion therein, without disturbing the substance.

In some embodiments, use detection by the detector 218 may be performedby detecting structural changes occurring in the vial 400, or any one ofthe containers 104, upon use thereof. For example, the vial 400 may beformed with a cap 470. The removal of the cap 470 prior to use may bedetected by detector 218 and indicative of use of the substance. In somevials 400 upon removal of the cap 470, an underlying seal 474 bulges.The bulging of the seal 470 may be detected by detector 218 andindicative of use of the substance. In an additional example, underlyingthe cap 470 may be a threaded, external side surface 476 formed on thevial 400. Upon removal of cap 470, the transition from a smooth,external side surface 478 of the cap 470 to the threaded, external sidesurface 476 of the vial 400 may be detected by detector 218 andindicative of use of the substance. In yet an additional example, thetilting of the vial 400 or container 104 prior to removal of thesubstance may be detected by detector 218, which may comprise anaccelerometer, and may be indicative of use of the substance.

In some embodiments, the environmental control apparatus 140 maycomprise an upper protrusion 480 extending towards the vial 400 at a topportion 484 thereof and/or a lower protrusion 490 extending towards thevial 400 at a bottom portion 494 thereof. Upper protrusion 480 and/orlower protrusion 490 may be pressed while the vial 400 is within theenvironmental control apparatus 140 and may bulge upon removal of thevial 400 from the environmental control apparatus 140. The bulging ofthe upper protrusion 480 and/or lower protrusion 490 may be detected bydetector 218 and indicative of use of the substance.

The environmental control apparatus 140 of FIGS. 9 and 10 may comprisecommunication means 248 for transmitting information therefrom to thedevice 250 and/or central database 252.

FIGS. 11 and 12 each illustrate an exemplary substance control system100 according to some embodiments. In the embodiment of FIGS. 11 and 12the environmental control apparatus 140 may be configured as a tube 500comprising a first portion 512 and a second portion 514.

As seen in FIGS. 11 and 12 the environmental control element 150comprises passive temperature controlling elements, such as a layer ofthermal insulation 200.

In some embodiments, as seen in FIG. 11, the first portion 512 andsecond portion 514 comprise the thermal insulation 200. The thermalinsulation 200 may be formed in any suitable configuration, such as alayer of insulating material 520 at least partially underlying a cover530 and 532 of respective first and second portions 512 and 514.

In some embodiments, as seen in FIG. 12, the thermal insulation 200 maycomprise the insulating construction 280 including the two mutuallyinsertable inner and outer insulating enclosures 284 and 286, asdescribed in reference to FIG. 5. Thermal conductivity between theenvironmental control element 150 and the chamber 106 may be provided inany suitable manner.

In some embodiments, the environmental control apparatus 140 maycomprise the phase change material formed as layer 450 underlying atleast partially a layer of the thermal insulation 200.

In some embodiments, the phase change material layer 450 is obviatedfrom the environmental control apparatus 140 of FIGS. 11 and 12 and theenvironmental control element 150 may comprise thermal insulation 200only.

Covers 530 and/or 532 of the environmental control apparatus 140 may beformed of any suitable material, such as plastic. The covers 530 and/or532 may be formed of an opaque material for preventing penetration oflight therein.

FIGS. 13-15 illustrate an exemplary substance control system 100according to some embodiments of the present disclosure. As seen inFIGS. 13-15, the container 104 comprises a cartridge 550 formed with thechamber 106 for containing a substance therein, such as a drug 110. Anexemplary cartridge may be configured to be inserted into a refillablepen injector 108 of FIG. 1A.

The environmental conditions of the drug 110 within the cartridge 550may be maintained and controlled by the environmental control apparatus140 formed in any suitable configuration, as described throughout thedisclosure. In the embodiment of FIG. 13, the environmental controlapparatus 140 may be formed as the tube 270 (FIG. 4) configured andsized for enclosing the cartridge 550. In the embodiment of FIG. 14, theenvironmental control apparatus 140 may be formed as the tube 278 (FIG.5) configured and sized for enclosing the cartridge 550. In theembodiment of FIG. 15, the environmental control apparatus 140 may beformed as the tube 300 (FIG. 6) configured and sized for enclosing thecartridge 550.

FIGS. 16 and 17 illustrate an exemplary substance control system 100according to some embodiments of the present disclosure. As seen in FIG.16, the container 104 comprises a vial or ampule 580 including thechamber 106 containing a substance (e.g. the drug 110) therein. Theampule 580 comprises walls 588 formed of any suitable material forhousing the chamber 106. Typically, the ampule 580 is configured as adisposable container.

In some embodiments, as seen in FIG. 16, the environmental controlapparatus 140 comprises the ECM 162 including the TEC or any otheractive temperature controlling element. In some embodiments, the ECM 162may comprise a metallic strip, for example. The walls 588 may be formedwith thermal insulation 200, such as a thermal insulating materialcomprising glass, for example. The ECM 162 may be placed at any suitablelocation for thermal and/or mechanical contact with the chamber 106. Asseen in FIG. 16, the ECM 162 is mounted within an aperture 590 formedwithin the wall 588, thereby excluding the thermal insulation 200 at theaperture 590 and allowing thermal contact between the ECM 162 and thechamber 106.

In the embodiment of FIG. 16 the ECM 162 is placed at a bottom portion594 of the ampule wall 588, it being appreciated that the ECM 162 may beplaced at the sides of wall 588.

The ECM 162 may be connected to a heat dissipater 190 comprising a heatsink element 600 placed at any suitable location, such as within a base610. The ampule 580 may be mounted on base 610 and engaged therewith inany suitable manner such as by attachment means 614 which may be formedof a thermally conductive material as well as for attachment of the ECM162 to the base 610, such as a magnet for example.

A power source, such as a battery 164 and the controller and electronics166 may be embedded, or included in any suitable manner, within the base610 as well as electrical communication between the battery 164 and thecontroller and electronics 166 and the ECM 162. Detectors 218, timers220 and/or indicators 222 may be provided and placed on base 610.

At least one or more substance temperature sensors 184 may be providedin proximity to the chamber 106 and/or at least one or more ambienttemperature sensors 186 may be provided in proximity to the ambientenvironment at any suitable location, such as on the wall 588 inproximity to the ambient environment, or on the base 610, for example.

The environmental control apparatus 140 may comprise communication means248 for transmitting information therefrom to the device 250 and/orcentral database 252. The communication means 248 may be placed at anysuitable location, such as within the base 610.

In some embodiments, the battery 164 may be rechargeable. Recharging maybe performed via recharging port 168, or via inductance or other meanswhich allow electrical charge generation. The recharging port 168 may beplaced at any suitable location, such as within the base 610.

As seen in FIG. 16, the environmental control apparatus 140 comprisesthe ECS. The ECS includes the ECM 162 and base 610 which are configuredfor mechanically fitting the ampule 580.

In FIG. 16 a single ampule 580 and environmental control apparatus 140are shown. Turning to FIG. 17, it is seen that the substance controlsystem 100 may comprise an ampule holder or tray 630 for holding aplurality of ampules 580 therein. A plurality of environmental controlapparatuses 140 including the ampules 580 and corresponding bases 610may be mounted on the tray 630 or in some embodiments, the bases 610 maybe embedded within the tray 630.

In some embodiments, the tray 630 may comprise a single recharging port168 for recharging the battery 164 of the plurality of bases 610. Insome embodiments, the tray 630 may comprise a single battery 164 used toprovide power to each environmental control apparatus 140 and the tray630 may further comprise electrical contacts with the ECM 162.

The active temperature controlling elements, such as the ECM 162described in reference to FIGS. 1A-25, may be operated in any suitablemanner. In some embodiments, the active temperature controlling elementmay operate substantially continuously during use of the environmentalcontrol apparatuses 140. In this continuous operational mode the ECM 162is continuously operated to maintain the substance within thepredetermined range (or below or above a predetermined threshold). Thebattery 164 or any other power source continuously operates as well, toprovide power to the ECM 162 and the other electronics 166.

In some embodiments, the active temperature controlling element mayoperate selectively (i.e. a “thermostat” mode). In this selectiveoperational mode the controller 166 may monitor the environmentalcondition (e.g. temperature) within the substance (e.g. drug 110) in aclosed-loop circuit. Upon detection that the environmental conditiondeviated from the predetermined threshold or range, the ECM 162 isactivated until the environmental condition returns to the predeterminedthreshold or range. Thereafter the ECM 162 may be deactivated until onceagain the environmental condition deviates from the predeterminedthreshold or range. During the selective operational mode the battery164, or any other power source, can operate in response to the selectiveoperation of the ECM, such that during time periods that the ECM 162 isinactive the electronics 166 may be inactive as well, or may operatewith relatively low current. Thus this selective operational modefacilitates conservation of power. Yet, at time periods wherein the ECM162 is inactive, heat may penetrate the chamber 106 via the ECM 162and/or thermal transmitter 170, which is in thermal and/or mechanicalcontact with the ECM 162.

As seen in FIGS. 18A-19B, in order to prevent the heat penetration, athermal switch 650 may be configured to selectively connect ordisconnect the ECM 162 from chamber 106. The thermal switch 650 maycomprise any suitable mechanism configured for selective contact inresponse to detection of deviation from the predetermined threshold orrange. In some embodiments, as seen in FIGS. 18A-19B, the thermal switch650 may comprise two adjacent first and second respective protrusions654 and 658. The first protrusion 654 may extend from ECM 162 towardsthe second protrusion 658, which may extend from the thermal transmitter170 or chamber 106. In the embodiment of FIGS. 18A and 18B, the firstand second respective protrusions 654 and 658 may comprise magneticproperties. According to the direction of the electrical current of theelectronics circuit, the protrusions 654 and 658 may be mutuallyattracted thereto. This attraction provides thermal contact between theECM 162 and the thermal transmitter 170, upon activation of the ECM 162,as seen in FIG. 18A.

Whereupon the ECM 162 is inactive, the direction of the current may bedirected to cause protrusions 654 and 658 to repel, thereby thermallydisconnecting the ECM 162 from the thermal transmitter 170, as seen inFIG. 18B.

The protrusions 654 and 658 may be formed at least partially withmagnetic properties or may comprise respective first and second magneticstrips 660 and 662 or other configurations. Any one of the first andsecond magnetic strips 660 and 662 may comprise a static magnet or anelectromagnet paired with a corresponding electromagnet and/or the firstand second magnetic strips 660 and 662 may comprise a ferromagneticmaterial.

Protrusions 654 and 658 may be configured of a flexible materialallowing the protrusions 654 and 658 to contact each other uponattraction of the magnetic strips 660 and 662.

Turning to FIGS. 19A and 19B it is seen that the thermal switch 650 maycomprise first and second respective protrusions 664 and 668 formed withan air gap 670 defined therebetween. On the first and/or secondrespective protrusions 664 and 668 there may be provided a suitablematerial that can expand and contract, such as a spring 680. Uponextension of the spring 680 the gap 670 fills, thereby connecting theECM 162 to the thermal transmitter 170 or chamber 106, as seen in FIG.19A. Upon contraction of the spring 680 the gap 670 vacates, therebydisconnecting the ECM 162 from the thermal transmitter 170 or chamber106, as seen in FIG. 19B.

Further modes of operation and control of ECM 162 may be as follows: forexample, in some embodiments, an electrical “gate”, i.e., a transistor,is provided for supply of a current to an active temperature controllingelement, such as a thermoelectric heat-pump, upon the temperature of thedrug deviating from the predetermined threshold or range. Such apredetermined threshold or range may be established by the electricalparameters of the electrical circuit of electronics 166. This method mayprovide for a simple realization of a “gate” without a controller (whichmay be inexpensive and with lower power requirements). Any form ofelectrical circuit, analog or digital, may be used to control the powerprovided to the ECM 162 to effect a change in at least one environmentalcondition. Such circuits may utilize temperature sensors, such assensors 184 and/or 186.

In some embodiments, the flow of power from the power source to the ECM162 is determined based upon the temperature of the interior of the ECSsensed by the substance sensor 184.

In some embodiments, the ECM 162 may be configured to cool the drug 110when the temperature inside the ECS is above the predetermined range toa temperature within the range. The ECM 162 may be further configured toheat the drug 110 when the temperature inside the ECS is below thepredetermined range to a temperature within the predetermined range.

In some embodiments, the parameters of the electronic circuit may bechosen such that no current flows to the ECM 162 from the power sourceas long as the temperature of the of the substance within the chamber106 is within the predetermined range or threshold. Whenever thetemperature is out of this range or above or below the threshold,current is permitted to flow to cause the ECM 162 to effect a change inthe temperature that is to increase or reduce the temperature untilreaching the predetermined threshold or range, while the currentprovided to the ECM 162 is substantially reduced or shut off.

In any one of the environmental control apparatuses 140 described inreference to FIGS. 1A-25 comprising the active temperature controllingelements, such as the TEC, there may be provided an activation element690 (FIG. 1A) to activate the ECM 162 upon detecting that the substance(e.g. drug 110) was inserted into the chamber 106. Thus, unnecessary useof the battery 164 is prevented.

In a non-limiting example, it was found that 0.33 W is sufficient powerto activate the environmental control apparatus 140 comprising a tubesimilar to tube 240 of FIG. 2 for maintaining a substance of 3 cc ofwater at a required temperature of 8 C.°, while the environmentalcontrol apparatus 140 is placed at ambient temperature of 24 C.°.Accordingly, to operate the environmental control apparatus 140 for aperiod of 24 hours, the required energy will be: 0.33 W×3600 second×24hours=28,512 Joules, which is less than the total energy provided by astandard 3.6-volt Lithium-ion battery, rated at 2,500 mAh as having atotal energy of 32,400 Joules.

In some embodiments, any one of the environmental control apparatuses140 described throughout the disclosure may comprise the controller 166comprising a processor for controlling the ECM 162. The processor mayinclude computer instructions comprising an algorithm operating thereonconfigured to control the ECM 162. In some embodiments, the algorithmmay be configured to automatically control the temperature of the drug110 contained within the DDSD, to be maintained within the predeterminedrange. In some embodiments, the algorithm may be configured to controlthe temperature while minimizing a thermal load created by the operationof the ECM 162.

FIG. 20 is a schematic illustration of an exemplary substance controlsystem 100 according to some embodiments of the present disclosure. Asseen in FIG. 20, the environmental control apparatus 140 may beconfigured to control and maintain the environmental condition of morethan one substance and/or a substance at different phases. The containermay comprise an injection pen 700 formed with at least two chambers 106including a first storage chamber 702 and a second delivery chamber 704.

A first substance 712 may be contained in the first storage chamber 702at a first phase and then, typically prior to delivery, or at any othersuitable time, may be mixed with a second substance contained in thesecond delivery chamber 704. In a non-limiting example, the firstsubstance 712 may comprise a drug 110 in powder form. The secondsubstance 714 may comprise a mixing liquid or a mixing element fordissolving the powder when mixed therewith to provide a liquid drugpreparation for delivery to a human or animal. In some embodiments, thesecond substance 714 may comprise a gas for gasifying the powder.

In a non-limiting example the drug 110 may be volatile when stored at aliquid phase. Therefore, the drug 110 may be first stored in a powderphase and prior to delivery, can be liquefied. Such a drug may includeglucagon.

The first substance 712 and/or second substance 714 may be contained ina suitable receptacle, such as in plastic packets, for example. In someembodiments, the first substance 712 and/or second substance 714, whenin powder form for example, may be encapsulated within a capsule 720.Capsule 720 may be formed of any suitable material. In some embodiments,the capsule 720 may be formed of a material with physical propertiessimilar to aluminum, which does not interact or otherwise affect thedrug 110. The capsule material may be formed of an opaque material forpreventing penetration of light therein. The capsule 720 may also beformed of a heat conducting material such as, for example, a foil, andmay be evacuated for air tight encapsulation and for preventing exposureto humidity.

In some embodiments, such as shown in FIG. 20, the capsules 720 may bestored within the first chamber 702 and the mixing liquid may becontained within the second chamber 704. The pen 700 may be prefilledwith the capsules 720 and/or the mixing liquid, typically in adisposable pen.

In some embodiments, the pen 700 may be configured to receive thecapsules 720 such as by providing an opening (not shown) to insert thecapsules within the first chamber 702. The pen 700 may be additionallyconfigured to receive the mixing liquid such as by providing an opening(not shown) to insert the mixing liquid within the second chamber 704,typically in a reusable pen. The capsules 720 may be pierced by a needle722 of the injection pen and pushed by a plunger of a piston 724 intothe second delivery chamber 704 to mix with the mixing liquid fordissolving the powder.

In some embodiments, the dissolved drug preparation may be introducedinto an additional chamber (not shown) and may be delivered to the humanor animal from the additional delivery chamber. Additional mixing of thepowder and the mixing liquid and/or filtering may be performed withinthe additional chamber prior to delivery thereof.

In some embodiments, several drug capsules containing a drug in powderedform are placed within the first chamber 702. A single or a few capsulesmay be used at a particular time. A second capsule (or additionalcapsules) may be punctured and mixed with at least the mixing liquidwhenever an additional dose of drug is required.

The injection pen 700 may be disposable or reusable. The environmentalcontrol apparatus 140 may be placed within the injection pen 700 aroundthe first storage chamber 702 and/or the second delivery chamber 704, orin proximity thereto and may be configured to control and maintain theenvironmental conditions of the substance in the first storage chamber702 and/or the second delivery chamber 704.

The environmental control apparatus 140 may comprise a first enclosure730 enclosing the first chamber 702 and/or a second enclosure 732enclosing the second chamber 704. The first enclosure 730 and/or secondenclosure 732 (if provided) may include the ECM 162 comprising the TECor any other active temperature controlling elements. The firstenclosure 730 and/or second enclosure 732 may be formed of the thermalinsulation 200. In some embodiments, the thermal insulation 200 maycomprise the multi-layered material, formed of walls 202 and 204 withthe evacuated gap 206 therebetween. The ECM 162 may be placed at anysuitable location for thermal and/or mechanical contact with the firstchamber 702. As seen in FIG. 20, the ECM 162 is mounted within anaperture 734 formed within the first enclosure 730 and/or secondenclosure 732, thereby excluding the thermal insulation 200 at theaperture 734 and allowing thermal contact between the ECM 162 and thechamber 106.

At least one or more substance temperature sensors 184 may be providedin proximity to at least one of the first storage chamber 702 and/or thesecond delivery chamber 704 and/or at least one or more ambienttemperature sensors 186 may be provided in proximity to the ambientenvironment at any suitable location, such as on the injection pen 700.

Heat may be dissipated by heat dissipater 190 forming at least a portionof a cover or ring 740 surrounding the pen injector 700. In someembodiments, heat dissipating fins 196 or any other heat dissipatingelement may be provided. In some embodiments, the heat dissipater 190may comprise a heat sink element 750 placed within the pen injector 700.The heat may be removed from the ECM 162 via the piston 724 configuredfor thermal conduction for conducting heat to heat sink element 750.Additional methods for removing/adding heat from/to the first storagechamber 702 and/or the second delivery chamber 704 may be used,including, for example, micro-fans and/or heat sink elements. Amicro-fan 756 may be placed within the pen 700.

In some embodiments, such as wherein all the first substance is directedfrom the first chamber 702 to the second chamber 704, the environmentalcontrol apparatus 140 may be configured to cease control by the ECM 162of the first enclosure 730 and to activate the previously dormant ECM162 of the second enclosure 732.

In embodiments wherein a portion of the first substance is directed fromthe first chamber 702 to the second chamber 704 and a portion remainswithin the first chamber 702, the environmental control apparatus 140may be configured to continue control by ECM 162 of the first enclosure730 and to activate the previously dormant ECM 162 of the secondenclosure 732.

In some embodiments, the capsule 720 may be stored within anenvironmental control apparatus 140 external to the pen 700 andthereafter may be introduced into pen 700. Such an apparatus may beformed as an enclosure 770, similar to respective first or secondenclosures 730 and 732 or as any one of the environmental controlapparatuses 140 disclosed herein.

In some embodiments, the environmental condition in the first chamber702 may be maintained at a different degree than the second chamber 704.For example, the temperature maintained within the first chamber 702 maybe a storage temperature, which may be lower than the temperaturemaintained within the second chamber 704, maintained at a usetemperature.

The battery 164 and the controller and electronics 166 may be embedded,or otherwise contained, within the first enclosure 730 or secondenclosure 732 or within the injection pen 700, or within a cap 760covering the injection pen 700, similar to the embodiment shown in FIG.7. The cap 760 may comprise electrical contacts 766 for electroniccommunication with corresponding electrical contacts 768 of the firstenclosure 730 and/or second enclosure 732. In some embodiments, theenvironmental control apparatus 140 and/or the pen 700 may comprise oneor more detectors 218, timers 220 and/or indicators 222 placed in anysuitable location, such as in the cap 760

In some embodiments, the environmental control apparatus 140 of any oneof FIGS. 1A-25, may be configured to maintain the substance at differentdegrees of the environmental condition. In some embodiments, thesubstance (e.g. a drug 110) may be maintained at a first temperature ortemperature range for a first time duration and thereafter maintained ata second temperature or temperature range for a second time duration.For example, the environmental control apparatus 140 may be configuredto maintain the drug 110 at a storage temperature or range, wherein thedrug 110 is in a storage state. Thereafter, prior to delivery of thedrug, the drug temperature may be changed to a use temperature or rangeto bring the drug 110 to a use state thereof.

The indicator 222 may be configured to indicate to the user the currentstate of the drug 110, i.e. a storage state or use state.

The detection of use may be performed in any suitable manner, such asdescribed in reference to FIG. 1A.

In some embodiments, a state switch 800 (FIG. 1A) may be provided andmay be configured in any suitable configuration for effecting the shiftfrom the storage temperature to the use temperature. In someembodiments, the shift may be reversible such that the temperature ofthe drug 110 may be shifted from use temperature back to storagetemperature. In some embodiments, the environmental control apparatus140 may be configured to affect the shift from the storage temperatureto the use temperature and prevent reversal back to the previous storagetemperature.

In some embodiments, the shift from the storage temperature to the usetemperature may be performed manually by a user. In some embodiments,the shift from the storage temperature to the use temperature may beperformed automatically upon detection of use by the detector 218. Insome embodiments, the shift from the storage temperature to the usetemperature may be based upon a predetermined program for setting thestorage temperature range and the storage time span and the usetemperature range and the use time span. The predetermined program maybe governed by the controller 166.

In some embodiments, the ECS may be configured to control theenvironmental condition according to at least one of a first storagestate configured to retain the drug 110 contained in the DDSD at theenvironmental condition within a first predetermined range, and a usestate configured to retain the drug contained in the DDSD at theenvironmental condition within a second predetermined range. Prior tothe first use of the DDSD, the environmental condition of the drug maybe maintained at the storage state and after first use of the DDSD, theenvironmental condition of the drug may maintained at the use state. Insome embodiments, the use state may be activated via the switch 800 orautomatically upon the first use of the DDSD.

In a non-limiting example, the drug 110 may comprise insulin and may bedelivered by an injection pen, such as injection pen 108 of FIG. 1A. Theenvironmental control apparatus 140 may be configured to maintain thedrug 110 at a storage temperature range of 2 C0 to 8 C.°, for arelatively long time span, such as a number of hours, days, months oreven years. Thereafter, prior to delivery of the drug, the drugtemperature may be changed to a use temperature in the range of 22 C.°to 24 C.° for a time span of minutes to a few hours.

In some embodiments, while in the storage state, activity of thecontroller and electronics 166 is reduced. Thus, unnecessary use of thebattery 164 is prevented.

In some embodiments, a first environmental control apparatus 140 may beconfigured to maintain and control the substance at a storage state.Upon transition to a use state the container 104 may be removed from thefirst environmental control apparatus 140 and placed within a secondenvironmental control apparatus 140, configured to maintain and controlthe substance at a use state.

FIGS. 21 and 22 are a schematic illustration of an exemplary substancecontrol system 100 according to some embodiments of the presentdisclosure. As seen in FIG. 21, a casing 820 is provided for encasingthe environmental control apparatus 140 and a container 104. In theembodiment of FIG. 21 the container 104 comprises the vial 400 and theenvironmental control apparatus 140 is formed of the tube 410 of FIG. 9,it being appreciated that the casing 820 may be used with any container104 and environmental control apparatus 140.

The casing 820 may be formed as a carrying case, which may betransportable, and may be formed of a relatively small size for easyplacement within a bag, handbag, backpack etc. The casing 820 maycomprise the environmental control element 150, such as passive controlelements, e.g. a material 826 formed of thermal insulation 200configured in any suitable manner as described herein.

In some embodiments, the environmental control element 150 mayadditionally comprise an active control element, such as the ECM 162.

In some embodiments, the casing 820 may comprise a phase change layer828 formed as layer 260 (FIG. 3) underlying at least partially a layerof the thermal insulation 826.

The container 104 may be encased in the casing 820 for a relatively longtime period such as hours, days, weeks, months or years. In anon-limiting example, the substance within the container 104 may bemaintained at a temperature which is significantly different than theambient temperature outside the casing 820. In a non-limiting example,the drug can be maintained within the casing 820 at a temperature rangeof about 2 C.° to 8 C.°, while the ambient temperature can be around 25C.° or the drug in the container 104 can be maintained at a temperaturerange of about 19 C.° to 25 C.° while the ambient temperature can beabout minus 10 C.° to 50 C.°.

In some embodiments, the casing 820, encasing the container 104 andenvironmental control apparatus 140, may be placed in a refrigerator andmay be used as a means of precaution in case the refrigerator is notpowered, such as during a power out.

In some embodiments, the casing 820 may comprise at least one or moresubstance temperature sensors 184 provided in proximity to the chamber106 or in thermal contact with the chamber 106. In some embodiments, thecasing 820 may comprise at least one or more ambient temperature sensors186 placed in proximity to the ambient environment at any suitablelocation, such as on a cover 860 of the casing 820.

The environmental control apparatus 140 may comprise communication means248 for transmitting information therefrom to the device 250 and/orcentral database 252. The communication means 248 may be placed in anysuitable location, such as at a base portion 862 of casing 820. Thecommunication means may comprise a port and/or transceiver, such as awireless transceiver or a wired transceiver.

A power source, such as a battery 864 (comprising battery 164 of FIG. 9)and the controller and electronics 866 (comprising controller andelectronics 166 of FIG. 9) may be embedded within base portion 862, orincluded in any suitable manner, within the casing 820. There also maybe included electrical communication between the battery 864 and thecontroller and electronics 866. In some embodiments, the battery 864 mayprovide power to the ECM 162 and controller and electronics 166 withinthe environmental control apparatus 140. The battery 864 may be providedin addition to battery 164 as a supplementary power source or thebattery 864 may replace battery 164.

In some embodiments, the battery 864 may be rechargeable. Recharging maybe performed via a recharging port 868, or via inductance or other meanswhich allow electrical charge generation. The recharging port 868 may beplaced at any suitable location, such as in base portion 862.

Heat may be dissipated by heat dissipater 190 forming at least a portionof the cover 860, which may be formed with a smooth surface or a surfaceconfigured with formations thereon (so as to function as a heat sink).Additional methods for removing heat from the ECM 162 may be used,including, for example, micro-fans and/or heat sink elements.

The casing 820 may be formed with a lid 870 for allowing insertion ofthe environmental control apparatus 140 and the container 104 thereinand removal therefrom. The casing 820 may be air-tight.

The casing 820 may comprise one or more detectors 218, timers 220 and/orindicators 222.

In FIG. 21 a single casing 820 and environmental control apparatus 140are shown. Turning to FIG. 22, it is seen that a plurality of casings820 may be coupled to each other by any suitable means. In someembodiments, the casing 820 may be formed with attachment means 880mounted on the cover 860. The attachment means 880 may comprise aprotrusion 882 configured to mate with a recess 884 formed in acorresponding attachment means of an adjacent casing 820. In someembodiments, the attachment means may include an electrical attachmentand/or a magnetic attachment or any other suitable configuration.

In some embodiments, the casing 820 may be configured to be stackablewith additional casings 820.

The coupling of a plurality of casings 820 allows for portability of theplurality of containers 104 while maintaining the substance thereinunder the predetermined environmental conditions. In some embodiments,charging the power sources, e.g. the batteries 164 of the plurality ofenvironmental control elements 140, may be facilitated simultaneously bya single or a few recharging means. In some embodiments, the rechargingmay be performed by a recharging port 890 configured to simultaneouslyrecharge the power sources of the plurality of environmental controlelements 140 and/or the plurality of casings 820. In some embodiments,the charging may be performed in any suitable manner, such as by wiredelectrical connections, by wireless connections such as by inductioncharging or any suitable manner.

In some embodiments, a single or a few power sources, e.g. a battery892, may be provided to power the plurality of environmental controlelements 140 and/or the plurality of casings 820.

FIG. 23 is a schematic illustration of an exemplary substance controlsystem 100 according to some embodiments of the present disclosure. Asseen in FIG. 23, the substance, comprising a drug 110, may be deliveredby infusion. A drug infusion device 900 comprises a catheter 906 formed,on one end thereof, with a cannula 908, which can be inserted into ahuman or animal tissue. In some embodiments, a connector 910 can connectthe catheter 906 to the tissue. Catheter 906 can be connected to thedrug chamber 106 and to an infusion pump 920, provided for control ofthe drug delivery from the chamber 106.

In some embodiments, an environmental control apparatus 140 may beprovided. As seen in FIG. 23, the environmental control apparatus 140may comprise an enclosure 930, configured substantially as the enclosure396 of FIG. 8. The enclosure 930 comprises the environmental controlelement 150 including any passive control element, such as the layer ofthermal insulation 200 for shielding the chamber 106 from the ambientenvironmental conditions. The phase change material layer 260 may beprovided and, at least partially, underlie the thermal insulation 200.

In some embodiments, the environmental control element 150 may compriseactive control elements (e.g. ECM 162) and the enclosure 930 and/or thedrug infusion device 900 may include a power source and the controllerand electronics, as described herein in reference to the enclosure 356of FIG. 7.

In some embodiments the drug infusion device 900 may comprise at leasttwo chambers (not shown), where at least a first chamber contains thedrug 110 in liquid form, while the second or more chambers, can containa liquid, another drug, or liquid to be mixed with a drug powder. Forexample, one drug may be insulin while the other may be glucagon. Theenclosure 930 may enclose the first chamber and/or second chamber forcontrolling and maintaining the environmental condition therein.

In some embodiments, the drug infusion device 900 may comprise atubeless or patch pump like the OmniPod of InsuLet or a tubed pump suchas the Medtronic Minimed Paradigm insulin pump.

In some embodiments, various components of the drug infusion device 900,such as one or more of the catheter 906, and pump 920, may be thermallyinsulated by the thermal insulation 200 described herein.

FIG. 24 is a schematic illustration of an exemplary substance controlsystem 100 according to some embodiments of the present disclosure. Asseen in FIG. 24, the substance may comprise a drug 110 formed as pills938 and the container 104 may comprise a standard pill dispenser 940,such as a tube or bottle, provided with a lid 942 and an opening 944.The chamber 106 may comprise the volume of the pill dispenser 940. Insome embodiments, the environmental control apparatus 140 may be formedas a ring 950 configured to be slipped on the pill dispenser 940.

The ring 950 may comprise the environmental control element 150including any passive control element, such as the layer of thermalinsulation 200 for shielding the chamber 106 from the ambientenvironmental conditions. The phase change material layer 260 may beprovided and, at least partially, underlie the thermal insulation 200.

In some embodiments, the environmental control element 150 may compriseactive control elements (e.g. ECM 162) and the ring 950 and/or the pilldispenser 940 may include a power source and the controller andelectronics, as described herein in reference to the enclosure 356 ofFIG. 7.

In some embodiments, various components of the pill dispenser 940, suchas the lid 942, may be thermally insulated by the thermal insulation 200described herein.

FIG. 25 is a schematic illustration of an exemplary substance controlsystem 100 according to some embodiments of the present disclosure. Asseen in FIG. 25, the substance may comprise a drug 110 formed as a fluidor powder and the container 104 may comprise an inhalator 960. Theinhalator 960 may comprise a drug chamber 106, which typically containsa pressurized drug.

In some embodiments, the inhalator 960 comprises a dispensing assemblyconfigured to remove the drug from the chamber 106, generally uponpressing the chamber 106. The drug is delivered via an opening formed inthe chamber 106 to an orifice (e.g. the mouth) of a user.

In some embodiments, an environmental control apparatus 140 may beprovided. As seen in FIG. 25, the environmental control apparatus 140may comprise an enclosure 970, configured substantially as the enclosure396 of FIG. 8. The enclosure 970 comprises the environmental controlelement 150 including any passive control element, such as the layer ofthermal insulation 200 for shielding the chamber 106 from the ambientenvironmental conditions. The phase change material layer 260 may beprovided and, at least partially, underlie the thermal insulation 200.

In some embodiments, the environmental control element 150 may compriseactive control elements (e.g. ECM 162) and the enclosure 970 and/or thedrug inhalator 960 may include a power source and the controller andelectronics, as described herein in reference to the enclosure 356 ofFIG. 7.

In some embodiments, any one of the environmental control apparatuses140 described in reference to FIGS. 1A-25 may include the dispensingassembly comprising an opening configured for allowing removal of thedrug 110 from the chamber 106 and delivering thereof to the patient viaan orifice provided with the patient (e.g. the user).

In some embodiments, any one of the environmental control apparatuses140 described in reference to FIGS. 1A-25 may comprise means forcontrolling the environmental conditions of a substance. In someembodiments, a predetermined humidity threshold or range may bemaintained and controlled, using any one of the environmental controlelements 150 described herein in reference to temperature control. Insome embodiments, the environmental control element 150 may compriseO-rings, sealants or any humidity absorbing element for maintaining andcontrolling the humidity of a substance.

In some embodiments, a predetermined pressure threshold or range may bemaintained and controlled using an environmental control element 150comprising a valve, insulation, O-rings or any element configured toprevent ambient pressure from entering the chamber 106.

In some embodiments, a predetermined light absorption threshold or rangemay be maintained and controlled using an environmental control element150 comprising an opaque cover or any material configured for preventinglight from penetrating the chamber 106.

In some embodiments, any one of the environmental control apparatusesdescribed in reference to FIGS. 1A-25 may exclude the environmentalcontrol element 150 and may just include any one of the featuresdescribed herein (e.g. detectors 218, timers 220 and/or indicators 222)

There are provided according to some embodiments of the presentdisclosure, systems and methods for calculating a quantity of thesubstance within the container 104 prior to or after delivery of thesubstance. The quantity may be measured in any suitable manner, such asthe mass, weight, volume or units of the substance, for example.

According to one method, the quantity of the substance may be calculatedby measurement of temperature changes, or other parameters related tothe temperature change, within the substance over a predetermined timespan. In some embodiments, the measurement of the temperature changes orthe other parameters, may be performed using any one of theenvironmental control apparatuses 140 described in reference to FIGS.1A-25.

In other words, the reading from the ambient temperature sensor 184(such as from the interior of the ECS) and the reading from the ambienttemperature sensor 186 may be used to determine the quantity of drug inthe DDSD and the quantity of drug removed from the DDSD.

For example, the quantity calculating system for calculating thesubstance quantity may include a clock, counter or timer 220 (FIG. 1A)configured to record the passage of time span “t” (i.e. duration) duringa predetermined temperature change “ΔT” (e.g. heating and/or cooling) ofthe substance. The quantity calculating system may additionally comprisethe substance temperature sensor 184 (FIG. 1A) for measuring thetemperature changes within the substance and the ambient temperaturesensor 186 for measuring the ambient temperature.

The initial quantity of the substance contained in the container 104 maybe known, such as the weight, denoted by “m₁”. The ambient temperaturesensor 186 may be used to measure the initial ambient temperature“T_(ai)” while the initial time “t_(i)” is recorded. At the same time,at t_(i), the substance temperature sensor 184 may measure the initialsubstance temperature “T_(si)”.

These measurements may be repeated and recorded until the substancetemperature changes by ΔT. In other words, these measurements may berepeated until the current measured substance temperature, T_(s)(t), haschanged from the initial substance temperature, T_(si), by ΔT, such thatat a final time “t_(f)” it is established that T_(s)(t)−T_(si)=ΔT.

In some embodiments, to ensure the ambient temperature is substantiallystable and constant during the repeated substance temperaturemeasurement, the ambient temperature is measured and compared to theinitial ambient temperature, T_(ai). Whereupon the current ambienttemperature T_(a)(t) is identical or substantially similar to theinitial ambient temperature T_(ai) (with some allowed deviation) therespective data generated by the substance measurement T_(s)(t), T_(si),ΔT, t_(i) and t_(f), will be recorded and utilized.

From these time recordings a first time span t, denoted by t₁, is foundthat: t₁=t_(f)−t₁ which is the time it takes for the substance underconstant heat flux to achieve the predetermined temperature change, ΔTat a first time span.

The substance temperature and ambient temperature measurements may berepeated and the time t₁ can further be averaged or recorded fordifferent substantially constant ambient temperatures. The result may bea table or any other form demonstrating an empirical relationshipbetween the time duration, t, it takes to achieve the predeterminedsubstance temperature change, ΔT, at a constant ambient temperature, anda series of constant ambient temperatures.

Following a change in the substance quantity, the measurements may berepeated as described hereinabove and a second time span t₂, whereint₂=t_(f)−t_(i) is recorded at a respective constant ambient temperature.

In some embodiments, the recorded times t₁ and t₂ and the correspondingtemperature measurements (e.g. T_(s)(t), T_(si), ΔT) may be utilized tocalculate the substance quantity in any suitable manner. In someembodiments, the averages of t₁ and t₂ may be calculated and thecorresponding temperature measurements may be utilized for calculatingthe substance quantity, according to the following non-limitingexemplary algorithm or in any other suitable manner:

The amount of energy “Q” required to change the temperature of asubstance by the predetermined temperature change ΔT is generallycalculated by:Q=mC _(p) ΔT  Formula 1:

Where m is the substance weight and C_(p) is the substance specific heatcapacity (specific heat).

Since it is established that: Q[joules]=Φ[watts]×t[sec]

The time for a substance to change its temperature by ΔT under constantheat flux Φ may be calculated byt=mC _(p) ΔT/Φ  Formula 2:

Hence, a change in the substance weight, while the other parameters areconstant, will result in a change of time span t it takes to achieve thesame change in temperature ΔT.

Whereupon the substance weight is reduced, which occurs following use ofthe substance, it will take a shorter time span t to achieve thespecific temperature change ΔT. The time span t can be found fromt ₁ =m ₁ C _(p) ΔT/Φ, t ₂ =m ₂ C _(p) ΔT/Φ

since t₂ is shorter than t₁ it satisfies t₂=t₁−Δt therefore Δt can beexpressed as:Δt=t ₁ −t ₂=(m ₁ −m ₂)C _(p) ΔT/Φ=ΔmC _(p) ΔT/Φ

The ratio t₂/t₁ it is then:t ₂ /t ₁=(t ₁ −Δt)/t ₁=1−Δt/t ₁=1−((ΔmC _(p) ΔT/Φ)×(Φ/m ₁ C _(p)ΔT))=1−Δm/m ₁

from this: Δm/m₁=1−(t₂/t₁) orΔm=m ₁(1−(t ₂ /t ₁))=m ₁((t ₁ −t ₂)/t ₁)

Or finally

${{\Delta\; m} = {m\; 1\frac{\Delta\; t}{t\; 1}}},$where Δt=t₁−t₂

Thus, the change in the substance quantity, such as the weight changeΔm, may be calculated based on the initial quantity, such as the initialweight m₁, and temperature measurements at that time. The substancequantity may further be calculated based on the time span t, it takes toachieve the predetermined change in temperature ΔT, during the initialsubstance quantity at time span t₁ and during a reduced substancequantity at time span t₂. This substance quantity calculation may beperformed without prior calibration, yet wherein the heat flux can beconsidered to be constant during the temperature measurements.

In some embodiments, the substance quantity may be calculated accordingto the above algorithm wherein the net heat flux in the environmentalcontrol apparatus 140 can modify the substance temperature by therequired temperature change ΔT within a finite time. Therefore acondition for the measurement may include:|Ta−Ts|>ΔT

Where Ta is the ambient temperature and Ts is the substance temperature.This condition may be fulfilled wherein the heat flux is constant duringthe time span t that it takes for the substance temperature to bemodified by ΔT. This same constant heat flux may occur also during thesubstance temperature change by ΔT. This generally occurs since usersmay use the substance while there is no immediate change in the ambienttemperatures. In practical terms, the time to achieve the ΔT change inthe substance temperature, should be longer than the activation time ofan active control element (e.g. the ECM 162) which is used to shift thesubstance temperature back from the current substance temperatureT_(s)(t) to the initial temperature T_(si).

In some embodiments, the constancy of the heat flux Φ may be affected bythe thermal insulation 200 of the container 104, by the ambienttemperature and by the setting point (e.g. the initial substancetemperature T_(si)) for activation.

The following is a non-limiting example of the algorithm describedabove. The results are shown in the graph of FIG. 26.

FIG. 26 is an exemplary graph showing the time t (in seconds) it takesfor a temperature change ΔT of water, measured in IU volume, to shift by3 C.°, assuming a drug reacts similarly to water. A volume of 3 cc ofwater (equaling 300 IU of insulin) was placed within a chamber 106. Thecontainer 104 was a syringe controlled by an environmental controlapparatuses 140 configured generally as shown in FIG. 4, wherein thethermal insulation 200 comprises walls 202 and 204 formed of INSULON®and an evacuated gap 206 therebetween of about 0.6 millimeters

The environmental control apparatus 140 was removed from refrigerationwherein the initial water temperature T_(si) was about 4 C.° and wasplaced in an ambient environment with a temperature of about 22 C.°.Thus, the difference between the ambient environment temperature and thesubstance temperature (T_(a)−T_(s)) was about 18 C.°. It was found thata time span of 1074 seconds passed (t=1074) to shift the temperature ΔTby 3 C.°, i.e. from 4 C.° to about 7 C.°. The water temperature wasmeasured by the temperature sensor 184 and the measured watertemperature is depicted by the dotted line.

FIG. 26 additionally shows the temperature detected by the ambientsensor 186 placed in proximity to cover 190. The measured ambienttemperature is depicted by the smooth line. It is seen that the ambienttemperature changed almost instantly, while a time span of 1074 secondspassed within the water to shift the water temperature by 3 C.°. This isdue to thermal insulation 200, the water heat capacity and volume.

FIG. 27 is an exemplary graph depicting the relationship of t Vs. thecalculated quantity of the water shown in the example of FIG. 26. Inthis example, the quantity comprises a volume and is measured in insulinunits (IU). It is seen that at about 1074 seconds the water quantity isabout 300 IU.

An exemplary graph depicting this relationship of the time span t Vs. ΔTis shown in FIG. 28 for a drug volume of 1 unit (IU) of Insulin, whichis 0.01 milliliters. It can be seen that even for such a small substancequantity, the time at each different temperature of the substance ismeasurable with relatively high precision.

To enhance accuracy of the measured time, t Vs. changes in temperature,ΔT, the measurements may be performed repeatedly at various times andconditions of use, such as prior to use of the substance or after use ofa portion of the substance, at various ambient environment temperatures,for example. The repeated measurements may be recorded and processed togenerate an accurate calculation of the substance quantity.

FIGS. 29 and 30 are an exemplary flowchart showing a process of analgorithm for performing the repeated measurements of temperature andtime to generate an accurate calculation of the substance quantity. FIG.29 illustrates a general process 1000 for executing an algorithm forrepeated calculations of the substance quantity and processing thereofand FIG. 30 illustrates a process 1001 for executing an algorithm for asingle or few calculations of the substance quantity.

As seen in FIG. 29, following initiation of the algorithm at step 1002it is verified at step 1004 whether the environmental control apparatus140 (i.e. “device”) is in use or docked or being recharged. If theenvironmental control apparatus 140 is docked, at step 1006 it ischecked whether data is being transferred, such as to device 250 (FIG.2) and/or central database 252. The data is transferred at step 1008until completion at step 1010.

If at step 1004 the environmental control apparatus 140 is in use, it isthereafter verified whether the container 104 is present in theenvironmental control apparatus 140, as seen at step 1014, allowing awaiting period at step 1018 until the container 104 is placed within theenvironmental control apparatus 140. If the container 104 is placedwithin the environmental control apparatus 140 a single quantity of thesubstance is calculated at step 1020 as further described in referenceto FIG. 30. Upon calculation of a single quantity the calculation isstored in any suitable memory device at step 1024.

If the container 104 is still maintained within the environmentalcontrol apparatus 140 the waiting period at step 1018 may be completedand the steps for calculating the substance quantity are repeated untilthe container 104 is removed from the environmental control apparatus140. Once the container 104 is detected as being removed at step 1028,the previous calculations stored at step 1024 may be processed forobtaining an accurate quantity measurement at step 1030. The processingmay include averaging the previous calculations, removal of noise or anyother method for processing results.

The processed, accurate, or otherwise improved, resultant quantity isstored at step 1034 and the process 1000 may commence once again at step1002.

Turning to FIG. 30 it is seen that at step 1050 the ambient environmenttemperature T_(ai) may be measured at a first time (e.g. the initialtime t_(i)), such as by ambient sensor 186. Thereafter, the initialtemperature T_(si) of the substance may be measured, such as bytemperature sensor 184, as seen at step 1054. The time t_(i) may bemeasured and stored at step 1058, as well as the measured ambientenvironment temperature T_(ai) and the temperature T_(si) of thesubstance. The time may be measured in any suitable manner, such as bytimer 220.

At step 1060 it is verified whether the temperature of the substanceshifted by the predetermined temperature change ΔT at time t_(f). If theshift did not occur, the substance temperature may be measured, as seenin steps 1054 and 1058. If the shift was effected, the ambientenvironment temperature T_(a)(t), may be measured at a second time (e.g.t_(f). or any given time), in step 1064.

At step 1068 the measured ambient environment temperatures T_(ai) andT_(a)(t) may be compared and the process may proceed if it is verifiedthat T_(ai) is substantially as in T_(a)(t), i.e. T_(a)(t)=T_(ai). Thisis to ensure the ambient environment temperature is stable whilemeasuring the substance temperature.

If T_(ai) and T_(a)(t) are dissimilar no calculation of the substancequantity is performed and the ECM 162 may be activated for returning thetemperature of the substance to the original temperature, prior to thetemperature change of ΔT. This may conclude the process 1001, as seen atstep 1069.

If T_(ai) is substantially as in T_(a)(t) at step 1070 the substancequantity may be calculated based on the stored time span t, such asaccording to Formula 2 described above. At step 1074 the calculatedsubstance quantity may be stored.

At step 1069 the ECM 162 may be activated for returning the temperatureof the substance to the original temperature, prior to the temperaturechange of ΔT. This may conclude the process 1001.

In some embodiments, The ECM 162 may be activated only once thesubstance temperature shifts by the predetermined temperature variationΔT.

The steps described in processes 1000 and 1001 may be interchangeableand some steps may be obviated.

It can be seen that by executing the algorithms of processes 1000 and1001 the substance quantity calculation may be repeated several times toimprove accuracy and record the amount of a substance which waspreviously used. Data can be recorded in a memory for later transfer bywired or wireless transmission to device 250 or to central database 252,such as described in reference to FIG. 2.

In addition to the substance quantity calculation system and methoddescribed in reference to FIGS. 26-30, the substance quantitycalculation may be performed by other systems and methods, such asdescribed as follows. In some embodiments, these systems and methods maybe combined with the system and method described in reference to FIGS.26-30.

In some embodiments, a substance quantity calculation system and methodmay comprise tracking the quantity of a dose of a delivered substanceand then subtracting it from a known initial quantity of substance priorto delivery of the substance (e.g., when the chamber 106 is initiallyfull).

In some embodiments, a substance quantity calculation system and methodmay include a measurement determined by at least one of sound (e.g.,ultrasound), impedance, and photo-acoustic measurement. For example,wherein the container is an injection pen 108 (FIG. 1A) measuring thephase or time of flight of a wave in the chamber 106 can provide thedistance from one side of the chamber 106 to the piston 118. Uponknowing the diameter of the chamber 106, the amount of substance thereincan be determined based on the discovered distance and known diameter.

In some embodiments, a substance quantity calculation system and methodmay include detecting a length by phase measurement where a transponderis tuned over a frequency range to sending and receiving ultrasoundwaves to detect a maximum signal at a predetermined frequency. Thewavelength corresponding to the maximum signal will relate to a distancebetween the transmitter and the receiver which is twice the length ofthe substance volume within the chamber 106. Thereby providing thelength still occupied with the substance and enabling calculation of theremaining substance volume. Additionally, potential measurement of theimpedance or other electrical properties of the substance, as well asthe distance between the edges of the chamber 106.

In some embodiments, a substance quantity calculation system and methodmay include providing a charge-coupled device (CCD) for imaging thelocation of a plunger of the piston 118 prior to delivery of thesubstance and following delivery thereof. The delivered substancequantity can be calculated by the resultant distance moved by theplunger.

While the disclosure has been described with respect to a limited numberof embodiments, it is to be realized that any combination of embodimentsin whole or part can also be used and that the optimum dimensionalrelationships for the parts of the invention, to include variations insize, materials, shape, form, function and manner of operation, assemblyand use, are deemed readily apparent and obvious to one skilled in theart, and all equivalent relationships to those illustrated in thedrawings and described in the specification are intended to beencompassed by the present invention.

Those of ordinary skill in the art will readily envision a variety ofother means and/or structures for performing the function and/orobtaining the results and/or one or more of the advantages describedherein, and each of such variations and/or modifications is deemed to bewithin the scope of the inventive embodiments described herein. Moregenerally, those skilled in the art will readily appreciate that allparameters, dimensions, materials, and configurations described hereinare meant to be an example and that the actual parameters, dimensions,materials, and/or configurations will depend upon the specificapplication or applications for which the inventive teachings is/areused. Those skilled in the art will recognize, or be able to ascertainusing no more than routine experimentation, many equivalents to thespecific inventive embodiments described herein. It is, therefore, to beunderstood that the foregoing embodiments are presented by way ofexample only and that, within the scope of the appended claims andequivalents thereto, inventive embodiments may be practiced otherwisethan as specifically described and claimed. Inventive embodiments of thepresent disclosure are directed to each individual feature, system,article, material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe inventive scope of the present disclosure. Some embodiments may bedistinguishable from the prior art for specifically lacking one or morefeatures/elements/functionality (i.e., claims directed to suchembodiments may include negative limitations).

Also, various inventive concepts may be embodied as one or more methods,of which an example has been provided. The acts performed as part of themethod may be ordered in any suitable way. Accordingly, embodiments maybe constructed in which acts are performed in an order different thanillustrated, which may include performing some acts simultaneously, eventhough shown as sequential acts in illustrative embodiments.

Any and all references to publications or other documents, including butnot limited to, patents, patent applications, articles, webpages, books,etc., presented anywhere in the present application, are hereinincorporated by reference in their entirety. Moreover, all definitions,as defined and used herein, should be understood to control overdictionary definitions, definitions in documents incorporated byreference, and/or ordinary meanings of the defined terms.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03.

What is currently claimed:
 1. A handheld, portable environmental controlsleeve configured for receiving an end of a drug delivery devicecomprising: an environmental control element (ECE) comprising: an openend, an interior volume, thermal insulation material formed at least ofa first exterior wall, and a second interior wall spaced away from thefirst exterior wall and defining an evacuated gap therebetween, whereinthe second interior wall defines the interior volume of the ECE, and aphase change material arranged outside of the evacuated gap; and atleast one of a power source, a processor, at least one electricalcontact, at least one indicator, at least one switch, at least onetemperature sensor, and a wireless transceiver, wherein: the interiorvolume of the ECE is configured to receive, via the open end, only areservoir end of the drug delivery device, the reservoir end having areservoir configured to contain a drug, the ECE further comprises matingmeans, arranged adjacent the open end and/or within the interior volume,and configured to mate with a corresponding feature of the reservoir endof the drug delivery device so as to removably retain only the reservoirend within the interior volume, and the ECE is configured to control thetemperature of the drug contained within the reservoir end receivedwithin the interior volume within the at least one predetermined range.2. The sleeve of claim 1, wherein the at least one predetermined rangecomprises at least two predetermined ranges.
 3. The sleeve of claim 2,wherein: the at least two predetermined ranges comprise a firstpredetermined range and a second predetermined range, and the ECE isconfigured to switch from controlling the temperature of the drugcontained within the reservoir to be within the first predeterminedrange to being within the second predetermined range.
 4. The sleeve ofclaim 1, wherein the at least one temperature sensor is configured tosense a temperature inside the sleeve.
 5. The sleeve of claim 1, whereinthe ECE is configured to control the temperature of the drug containedwithin the reservoir at above and/or below the at least onepredetermined range.
 6. The sleeve of claim 1, wherein the ECE isconfigured to perform at least one of: cooling the drug contained withinthe reservoir when a temperature inside the sleeve is above the at leastone predetermined range to a temperature within the at least onepredetermined range, and heating the drug contained within the reservoirwhen a temperature inside the sleeve is below the at least onepredetermined range to a temperature within the at least onepredetermined range.
 7. The sleeve of claim 1, wherein: the at least onepredetermined range comprises a first predetermined ranges and a secondpredetermined range, the ECE is configured to control the temperature ofthe drug contained within the reservoir according to at least one of: astorage state configured to retain the drug contained within thereservoir within the first predetermined range, and a use stateconfigured to retain the drug contained within the reservoir within thesecond predetermined range.
 8. The sleeve of claim 1, wherein prior to afirst use of the reservoir, the temperature of the drug contained withinthe reservoir is maintained at a storage state.
 9. The sleeve of claim1, wherein after a first use of the reservoir, the temperature of thedrug contained within the reservoir is maintained at a use state. 10.The sleeve of claim 1, wherein the mating means comprises a recessconfigured to receive a protrusion on the reservoir end of the drugdelivery device.
 11. The sleeve of claim 1, wherein the mating meanscomprises a protrusion configured for receiving by a recess on thereservoir end of the drug delivery device.
 12. The sleeve of claim 1,wherein the mating means comprises an interior volume shape of theinterior volume configured to mechanically correspond and fit thereservoir end of the drug delivery device.